In eukaryotes, general transcription factors (GTFs) enable recruitment of RNA polymerase II (RNA Pol II) to core promoters to facilitate initiation of transcription. Extensive research in mammals and yeast has unveiled their significance in basal transcription as well as in diverse biological processes. Unlike mammals and yeast, plant GTFs exhibit remarkable degree of variability and flexibility. This is because plant GTFs and GTF subunits are often encoded by multigene families, introducing complexity to transcriptional regulation at both cellular and biological levels. This review provides insights into the general transcription mechanism, GTF composition, and their cellular functions. It further highlights the involvement of RNA Pol II-related GTFs in plant development and stress responses. Studies reveal that GTFs act as important regulators of gene expression in specific developmental processes and help equip plants with resilience against adverse environmental conditions. Their functions may be direct or mediated through their cofactor nature. The versatility of GTFs in controlling gene expression, and thereby influencing specific traits, adds to the intricate complexity inherent in the plant system.
在真核生物中,一般转录因子(GTFs)能将 RNA 聚合酶 II(RNA Pol II)招募到核心启动子上,从而促进转录的启动。对哺乳动物和酵母的广泛研究揭示了它们在基础转录和各种生物过程中的重要作用。与哺乳动物和酵母不同,植物 GTFs 具有显著的变异性和灵活性。这是因为植物 GTFs 和 GTF 亚基通常由多基因家族编码,从而在细胞和生物水平上给转录调控带来了复杂性。本综述深入探讨了一般转录机制、GTF 的组成及其细胞功能。它进一步强调了与 RNA Pol II 相关的 GTFs 在植物发育和胁迫响应中的参与。研究表明,GTFs 是特定发育过程中基因表达的重要调控因子,有助于增强植物抵御不利环境条件的能力。它们的功能可能是直接的,也可能是通过其辅助因子介导的。GTFs 在控制基因表达从而影响特定性状方面的多功能性增加了植物系统固有的复杂性。
{"title":"The general transcription factors (GTFs) of RNA polymerase II and their roles in plant development and stress responses.","authors":"Shivam Sharma, Sanjay Kapoor, Athar Ansari, Akhilesh Kumar Tyagi","doi":"10.1080/10409238.2024.2408562","DOIUrl":"10.1080/10409238.2024.2408562","url":null,"abstract":"<p><p>In eukaryotes, general transcription factors (GTFs) enable recruitment of RNA polymerase II (RNA Pol II) to core promoters to facilitate initiation of transcription. Extensive research in mammals and yeast has unveiled their significance in basal transcription as well as in diverse biological processes. Unlike mammals and yeast, plant GTFs exhibit remarkable degree of variability and flexibility. This is because plant GTFs and GTF subunits are often encoded by multigene families, introducing complexity to transcriptional regulation at both cellular and biological levels. This review provides insights into the general transcription mechanism, GTF composition, and their cellular functions. It further highlights the involvement of RNA Pol II-related GTFs in plant development and stress responses. Studies reveal that GTFs act as important regulators of gene expression in specific developmental processes and help equip plants with resilience against adverse environmental conditions. Their functions may be direct or mediated through their cofactor nature. The versatility of GTFs in controlling gene expression, and thereby influencing specific traits, adds to the intricate complexity inherent in the plant system.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"267-309"},"PeriodicalIF":6.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Space exploration and research are uncovering the potential for terrestrial life to survive in outer space, as well as the environmental factors that affect life during interplanetary transfer. The presence of methane in the Martian atmosphere suggests the possibility of methanogens, either extant or extinct, on Mars. Understanding how methanogens survive and adapt under space-exposed conditions is crucial for understanding the implications of extraterrestrial life. In this article, we discuss methanogens as model organisms for obtaining energy transducers and producing methane in a simulated Martian environment. We also explore the chemical evolution of cellular composition and growth maintenance to support survival in extraterrestrial environments. Neutral selective pressure is imposed on the chemical composition of cellular components to increase cell survival and reduce growth under physiological conditions. Energy limitation is an evolutionary driver of macromolecular polymerization, growth maintenance, and survival fitness of methanogens. Methanogens grown in a Martian environment may exhibit global alterations in their metabolic function and gene expression at the system scale. A space systems biology approach would further elucidate molecular survival mechanisms and adaptation to a drastic outer space environment. Therefore, identifying a genetically stable methanogenic community is essential for biomethane production from waste recycling to achieve sustainable space-life support functions.
{"title":"Methanogens and what they tell us about how life might survive on Mars.","authors":"Chellapandi Paulchamy, Sreekutty Vakkattuthundi Premji, Saranya Shanmugam","doi":"10.1080/10409238.2024.2418639","DOIUrl":"10.1080/10409238.2024.2418639","url":null,"abstract":"<p><p>Space exploration and research are uncovering the potential for terrestrial life to survive in outer space, as well as the environmental factors that affect life during interplanetary transfer. The presence of methane in the Martian atmosphere suggests the possibility of methanogens, either extant or extinct, on Mars. Understanding how methanogens survive and adapt under space-exposed conditions is crucial for understanding the implications of extraterrestrial life. In this article, we discuss methanogens as model organisms for obtaining energy transducers and producing methane in a simulated Martian environment. We also explore the chemical evolution of cellular composition and growth maintenance to support survival in extraterrestrial environments. Neutral selective pressure is imposed on the chemical composition of cellular components to increase cell survival and reduce growth under physiological conditions. Energy limitation is an evolutionary driver of macromolecular polymerization, growth maintenance, and survival fitness of methanogens. Methanogens grown in a Martian environment may exhibit global alterations in their metabolic function and gene expression at the system scale. A space systems biology approach would further elucidate molecular survival mechanisms and adaptation to a drastic outer space environment. Therefore, identifying a genetically stable methanogenic community is essential for biomethane production from waste recycling to achieve sustainable space-life support functions.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"337-362"},"PeriodicalIF":6.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-10-08DOI: 10.1080/10409238.2024.2411264
Asrar Ahmad Malik, Mohd Shariq, Javaid Ahmad Sheikh, Udyeshita Jaiswal, Haleema Fayaz, Gauri Shrivastava, Nasreen Z Ehtesham, Seyed E Hasnain
Mycobacterium tuberculosis (M. tb) is one of the most successful human pathogens, causing a severe and widespread infectious disease. The frequent emergence of multidrug-resistant (MDR) strains has exacerbated this public health crisis, particularly in underdeveloped regions. M. tb employs a sophisticated array of virulence factors to subvert host immune responses, both innate and adaptive. It utilizes the early secretory antigenic target (ESAT6) secretion system 1 (ESX-1) type VII secretion system (T7SS) and cell wall lipids to disrupt phagosomal integrity, inhibiting phagosome maturation, and fusion with lysosomes. Although host cells activate mechanisms such as ubiquitin (Ub), Ub-ligase, and cyclic GMP-AMP synthase-stimulator of interferon genes 1 (CGAS-STING1)-mediated autophagy to inhibit M. tb survival within macrophages, the pathogen counteracts these defenses with its own virulence factors, thereby inhibiting autophagy and dampening host-directed responses. T7SSs are critical for transporting proteins across the complex mycobacterial cell envelope, performing essential functions, including metabolite uptake, immune evasion, and conjugation. T7SS substrates fall into two main families: ESAT-6 system proteins, which are found in both Firmicutes and Actinobacteria, and proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) proteins, which are unique to mycobacteria. Recent studies have highlighted the significance of T7SSs in mycobacterial growth, virulence, and pathogenesis. Understanding the mechanisms governing T7SSs could pave the way for novel therapeutic strategies to combat mycobacterial diseases, including tuberculosis (TB).
{"title":"Mechanisms of immune evasion by <i>Mycobacterium tuberculosis</i>: the impact of T7SS and cell wall lipids on host defenses.","authors":"Asrar Ahmad Malik, Mohd Shariq, Javaid Ahmad Sheikh, Udyeshita Jaiswal, Haleema Fayaz, Gauri Shrivastava, Nasreen Z Ehtesham, Seyed E Hasnain","doi":"10.1080/10409238.2024.2411264","DOIUrl":"10.1080/10409238.2024.2411264","url":null,"abstract":"<p><p><i>Mycobacterium tuberculosis</i> (<i>M. tb</i>) is one of the most successful human pathogens, causing a severe and widespread infectious disease. The frequent emergence of multidrug-resistant (MDR) strains has exacerbated this public health crisis, particularly in underdeveloped regions. <i>M. tb</i> employs a sophisticated array of virulence factors to subvert host immune responses, both innate and adaptive. It utilizes the early secretory antigenic target (ESAT6) secretion system 1 (ESX-1) type VII secretion system (T7SS) and cell wall lipids to disrupt phagosomal integrity, inhibiting phagosome maturation, and fusion with lysosomes. Although host cells activate mechanisms such as ubiquitin (Ub), Ub-ligase, and cyclic GMP-AMP synthase-stimulator of interferon genes 1 (CGAS-STING1)-mediated autophagy to inhibit <i>M. tb</i> survival within macrophages, the pathogen counteracts these defenses with its own virulence factors, thereby inhibiting autophagy and dampening host-directed responses. T7SSs are critical for transporting proteins across the complex mycobacterial cell envelope, performing essential functions, including metabolite uptake, immune evasion, and conjugation. T7SS substrates fall into two main families: ESAT-6 system proteins, which are found in both Firmicutes and Actinobacteria, and proline-glutamic acid (PE) and proline-proline-glutamic acid (PPE) proteins, which are unique to mycobacteria. Recent studies have highlighted the significance of T7SSs in mycobacterial growth, virulence, and pathogenesis. Understanding the mechanisms governing T7SSs could pave the way for novel therapeutic strategies to combat mycobacterial diseases, including tuberculosis (TB).</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"310-336"},"PeriodicalIF":6.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-10-21DOI: 10.1080/10409238.2024.2405476
Jian Hu, Yuhan Jiang
The Zrt/Irt-like protein (ZIP) family consists of ubiquitously expressed divalent d-block metal transporters that play central roles in the uptake, secretion, excretion, and distribution of several essential and toxic metals in living organisms. The past few years has witnessed rapid progress in the molecular basis of these membrane transport proteins. In this critical review, we summarize the research progress at the molecular level of the ZIP family and discuss the future prospects. Furthermore, an evolutionary path for the unique ZIP fold and a new classification of the ZIP family are proposed based on the presented structural and sequence analyses.
Zrt/Irt-like蛋白(ZIP)家族由普遍表达的二价d-受体金属转运体组成,在生物体内几种必需金属和有毒金属的摄取、分泌、排泄和分布过程中发挥着核心作用。过去几年,这些膜转运蛋白的分子基础研究进展迅速。在这篇重要综述中,我们总结了 ZIP 家族分子水平的研究进展,并讨论了未来的前景。此外,我们还根据所提供的结构和序列分析,提出了独特 ZIP 折叠的进化路径以及 ZIP 家族的新分类。
{"title":"Evolution, classification, and mechanisms of transport, activity regulation, and substrate specificity of ZIP metal transporters.","authors":"Jian Hu, Yuhan Jiang","doi":"10.1080/10409238.2024.2405476","DOIUrl":"10.1080/10409238.2024.2405476","url":null,"abstract":"<p><p>The Zrt/Irt-like protein (ZIP) family consists of ubiquitously expressed divalent <i>d</i>-block metal transporters that play central roles in the uptake, secretion, excretion, and distribution of several essential and toxic metals in living organisms. The past few years has witnessed rapid progress in the molecular basis of these membrane transport proteins. In this critical review, we summarize the research progress at the molecular level of the ZIP family and discuss the future prospects. Furthermore, an evolutionary path for the unique ZIP fold and a new classification of the ZIP family are proposed based on the presented structural and sequence analyses.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"245-266"},"PeriodicalIF":6.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1080/10409238.2024.2383408
Elizabeth G Reisman,Nikeisha J Caruana,David J Bishop
Mitochondria are essential, membrane-enclosed organelles that consist of ∼1100 different proteins, which allow for many diverse functions critical to maintaining metabolism. Highly metabolic tissues, such as skeletal muscle, have a high mitochondrial content that increases with exercise training. The classic western blot technique has revealed training-induced increases in the relatively small number of individual mitochondrial proteins studied (∼5% of the >1100 proteins in MitoCarta), with some of these changes dependent on the training stimulus. Proteomic approaches have identified hundreds of additional mitochondrial proteins that respond to exercise training. There is, however, surprisingly little crossover in the mitochondrial proteins identified in the published human training studies. This suggests that to better understand the link between training-induced changes in mitochondrial proteins and metabolism, future studies need to move beyond maximizing protein detection to adopting methods that will increase the reliability of the changes in protein abundance observed.
线粒体是一种重要的膜封闭细胞器,由 1100 多种不同的蛋白质组成,可发挥对维持新陈代谢至关重要的多种功能。新陈代谢旺盛的组织,如骨骼肌,线粒体含量很高,并随着运动训练而增加。经典的 Western 印迹技术显示,训练诱导了所研究的相对较少的线粒体蛋白质(占 MitoCarta 中超过 1100 种蛋白质的 5%)的增加,其中一些变化取决于训练刺激。蛋白质组学方法还发现了数百种对运动训练有反应的线粒体蛋白质。然而,在已发表的人体训练研究中,所发现的线粒体蛋白质几乎没有交叉,这令人惊讶。这表明,要想更好地了解训练诱导的线粒体蛋白质变化与新陈代谢之间的联系,未来的研究不仅需要最大限度地检测蛋白质,还需要采用能提高所观察到的蛋白质丰度变化可靠性的方法。
{"title":"Exercise training and changes in skeletal muscle mitochondrial proteins: from blots to \"omics\".","authors":"Elizabeth G Reisman,Nikeisha J Caruana,David J Bishop","doi":"10.1080/10409238.2024.2383408","DOIUrl":"https://doi.org/10.1080/10409238.2024.2383408","url":null,"abstract":"Mitochondria are essential, membrane-enclosed organelles that consist of ∼1100 different proteins, which allow for many diverse functions critical to maintaining metabolism. Highly metabolic tissues, such as skeletal muscle, have a high mitochondrial content that increases with exercise training. The classic western blot technique has revealed training-induced increases in the relatively small number of individual mitochondrial proteins studied (∼5% of the >1100 proteins in MitoCarta), with some of these changes dependent on the training stimulus. Proteomic approaches have identified hundreds of additional mitochondrial proteins that respond to exercise training. There is, however, surprisingly little crossover in the mitochondrial proteins identified in the published human training studies. This suggests that to better understand the link between training-induced changes in mitochondrial proteins and metabolism, future studies need to move beyond maximizing protein detection to adopting methods that will increase the reliability of the changes in protein abundance observed.","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":"17 1","pages":"1-23"},"PeriodicalIF":6.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-07-01DOI: 10.1080/10409238.2024.2369986
Morgan Kok, Jeffrey L Brodsky
The concentration of intracellular and extracellular potassium is tightly regulated due to the action of various ion transporters, channels, and pumps, which reside primarily in the kidney. Yet, potassium transporters and cotransporters play vital roles in all organs and cell types. Perhaps not surprisingly, defects in the biogenesis, function, and/or regulation of these proteins are linked to range of catastrophic human diseases, but to date, few drugs have been approved to treat these maladies. In this review, we discuss the structure, function, and activity of a group of potassium-chloride cotransporters, the KCCs, as well as the related sodium-potassium-chloride cotransporters, the NKCCs. Diseases associated with each of the four KCCs and two NKCCs are also discussed. Particular emphasis is placed on how these complex membrane proteins fold and mature in the endoplasmic reticulum, how non-native forms of the cotransporters are destroyed in the cell, and which cellular factors oversee their maturation and transport to the cell surface. When known, we also outline how the levels and activities of each cotransporter are regulated. Open questions in the field and avenues for future investigations are further outlined.
{"title":"The biogenesis of potassium transporters: implications of disease-associated mutations.","authors":"Morgan Kok, Jeffrey L Brodsky","doi":"10.1080/10409238.2024.2369986","DOIUrl":"10.1080/10409238.2024.2369986","url":null,"abstract":"<p><p>The concentration of intracellular and extracellular potassium is tightly regulated due to the action of various ion transporters, channels, and pumps, which reside primarily in the kidney. Yet, potassium transporters and cotransporters play vital roles in all organs and cell types. Perhaps not surprisingly, defects in the biogenesis, function, and/or regulation of these proteins are linked to range of catastrophic human diseases, but to date, few drugs have been approved to treat these maladies. In this review, we discuss the structure, function, and activity of a group of potassium-chloride cotransporters, the KCCs, as well as the related sodium-potassium-chloride cotransporters, the NKCCs. Diseases associated with each of the four KCCs and two NKCCs are also discussed. Particular emphasis is placed on how these complex membrane proteins fold and mature in the endoplasmic reticulum, how non-native forms of the cotransporters are destroyed in the cell, and which cellular factors oversee their maturation and transport to the cell surface. When known, we also outline how the levels and activities of each cotransporter are regulated. Open questions in the field and avenues for future investigations are further outlined.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"154-198"},"PeriodicalIF":6.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-05-22DOI: 10.1080/10409238.2024.2355885
Shane Stoeber, Holly Godin, Cheng Xu, Lu Bai
Chromatin is densely packed with nucleosomes, which limits the accessibility of many chromatin-associated proteins. Pioneer factors (PFs) are usually viewed as a special group of sequence-specific transcription factors (TFs) that can recognize nucleosome-embedded motifs, invade compact chromatin, and generate open chromatin regions. Through this process, PFs initiate a cascade of events that play key roles in gene regulation and cell differentiation. A current debate in the field is if PFs belong to a unique subset of TFs with intrinsic "pioneering activity", or if all TFs have the potential to function as PFs within certain cellular contexts. There are also different views regarding the key feature(s) that define pioneering activity. In this review, we present evidence from the literature related to these alternative views and discuss how to potentially reconcile them. It is possible that both intrinsic properties, like tight nucleosome binding and structural compatibility, and cellular conditions, like concentration and co-factor availability, are important for PF function.
{"title":"Pioneer factors: nature or nurture?","authors":"Shane Stoeber, Holly Godin, Cheng Xu, Lu Bai","doi":"10.1080/10409238.2024.2355885","DOIUrl":"10.1080/10409238.2024.2355885","url":null,"abstract":"<p><p>Chromatin is densely packed with nucleosomes, which limits the accessibility of many chromatin-associated proteins. Pioneer factors (PFs) are usually viewed as a special group of sequence-specific transcription factors (TFs) that can recognize nucleosome-embedded motifs, invade compact chromatin, and generate open chromatin regions. Through this process, PFs initiate a cascade of events that play key roles in gene regulation and cell differentiation. A current debate in the field is if PFs belong to a unique subset of TFs with intrinsic \"pioneering activity\", or if all TFs have the potential to function as PFs within certain cellular contexts. There are also different views regarding the key feature(s) that define pioneering activity. In this review, we present evidence from the literature related to these alternative views and discuss how to potentially reconcile them. It is possible that both intrinsic properties, like tight nucleosome binding and structural compatibility, and cellular conditions, like concentration and co-factor availability, are important for PF function.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"139-153"},"PeriodicalIF":6.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-07-11DOI: 10.1080/10409238.2024.2377094
Francesca Oppedisano, Salvatore Nesci, Anna Spagnoletta
Sirtuins (SIRTs) are a family of proteins with enzymatic activity. In particular, they are a family of class III NAD+-dependent histone deacetylases and ADP-ribosyltransferases. NAD+-dependent deac(et)ylase activities catalyzed by sirtuin include ac(et)ylation, propionylation, butyrylation, crotonylation, manylation, and succinylation. Specifically, human SIRT3 is a 399 amino acid protein with two functional domains: a large Rossmann folding motif and NAD+ binding, and a small complex helix and zinc-binding motif. SIRT3 is widely expressed in mitochondria-rich tissues and is involved in maintaining mitochondrial integrity, homeostasis, and function. Moreover, SIRT3 regulates related diseases, such as aging, hepatic, kidney, neurodegenerative and cardiovascular disease, metabolic diseases, and cancer development. In particular, one of the most significant and damaging post-translational modifications is irreversible protein oxidation, i.e. carbonylation. This process is induced explicitly by increased ROS production due to mitochondrial dysfunction. SIRT3 is carbonylated by 4-hydroxynonenal at the level of Cys280. The carbonylation induces conformational changes in the active site, resulting in allosteric inhibition of SIRT3 activity and loss of the ability to deacetylate and regulate antioxidant enzyme activity. Phytochemicals and, in particular, polyphenols, thanks to their strong antioxidant activity, are natural compounds with a positive regulatory action on SIRT3 in various pathologies. Indeed, the enzymatic SIRT3 activity is modulated, for example, by different natural polyphenol classes, including resveratrol and the bergamot polyphenolic fraction. Thus, this review aims to elucidate the mechanisms by which phytochemicals can interact with SIRT3, resulting in post-translational modifications that regulate cellular metabolism.
{"title":"Mitochondrial sirtuin 3 and role of natural compounds: the effect of post-translational modifications on cellular metabolism.","authors":"Francesca Oppedisano, Salvatore Nesci, Anna Spagnoletta","doi":"10.1080/10409238.2024.2377094","DOIUrl":"10.1080/10409238.2024.2377094","url":null,"abstract":"<p><p>Sirtuins (SIRTs) are a family of proteins with enzymatic activity. In particular, they are a family of class III NAD<sup>+</sup>-dependent histone deacetylases and ADP-ribosyltransferases. NAD<sup>+</sup>-dependent deac(et)ylase activities catalyzed by sirtuin include ac(et)ylation, propionylation, butyrylation, crotonylation, manylation, and succinylation. Specifically, human SIRT3 is a 399 amino acid protein with two functional domains: a large Rossmann folding motif and NAD<sup>+</sup> binding, and a small complex helix and zinc-binding motif. SIRT3 is widely expressed in mitochondria-rich tissues and is involved in maintaining mitochondrial integrity, homeostasis, and function. Moreover, SIRT3 regulates related diseases, such as aging, hepatic, kidney, neurodegenerative and cardiovascular disease, metabolic diseases, and cancer development. In particular, one of the most significant and damaging post-translational modifications is irreversible protein oxidation, i.e. carbonylation. This process is induced explicitly by increased ROS production due to mitochondrial dysfunction. SIRT3 is carbonylated by 4-hydroxynonenal at the level of Cys<sub>280</sub>. The carbonylation induces conformational changes in the active site, resulting in allosteric inhibition of SIRT3 activity and loss of the ability to deacetylate and regulate antioxidant enzyme activity. Phytochemicals and, in particular, polyphenols, thanks to their strong antioxidant activity, are natural compounds with a positive regulatory action on SIRT3 in various pathologies. Indeed, the enzymatic SIRT3 activity is modulated, for example, by different natural polyphenol classes, including resveratrol and the bergamot polyphenolic fraction. Thus, this review aims to elucidate the mechanisms by which phytochemicals can interact with SIRT3, resulting in post-translational modifications that regulate cellular metabolism.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"199-220"},"PeriodicalIF":6.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2024-05-21DOI: 10.1080/10409238.2024.2330372
Nina J Bonde, Alexander G Kozlov, Michael M Cox, Timothy M Lohman, James L Keck
The SSB protein of Escherichia coli functions to bind single-stranded DNA wherever it occurs during DNA metabolism. Depending upon conditions, SSB occurs in several different binding modes. In the course of its function, SSB diffuses on ssDNA and transfers rapidly between different segments of ssDNA. SSB interacts with many other proteins involved in DNA metabolism, with 22 such SSB-interacting proteins, or SIPs, defined to date. These interactions chiefly involve the disordered and conserved C-terminal residues of SSB. When not bound to ssDNA, SSB can aggregate to form a phase-separated biomolecular condensate. Current understanding of the properties of SSB and the functional significance of its many intermolecular interactions are summarized in this review.
大肠杆菌的 SSB 蛋白可在 DNA 代谢过程中的任何地方与单链 DNA 结合。根据条件的不同,SSB 有几种不同的结合模式。在发挥作用的过程中,SSB 会在 ssDNA 上扩散,并在 ssDNA 的不同区段之间快速转移。SSB 与许多其他参与 DNA 代谢的蛋白质相互作用,迄今已定义了 22 种这样的 SSB 相互作用蛋白质或 SIP。这些相互作用主要涉及 SSB 的无序和保守的 C 端残基。当 SSB 未与 ssDNA 结合时,可聚集形成相分离的生物分子凝聚物。本综述概述了目前对 SSB 特性及其多种分子间相互作用功能意义的理解。
{"title":"Molecular insights into the prototypical single-stranded DNA-binding protein from <i>E. coli</i>.","authors":"Nina J Bonde, Alexander G Kozlov, Michael M Cox, Timothy M Lohman, James L Keck","doi":"10.1080/10409238.2024.2330372","DOIUrl":"10.1080/10409238.2024.2330372","url":null,"abstract":"<p><p>The SSB protein of <i>Escherichia coli</i> functions to bind single-stranded DNA wherever it occurs during DNA metabolism. Depending upon conditions, SSB occurs in several different binding modes. In the course of its function, SSB diffuses on ssDNA and transfers rapidly between different segments of ssDNA. SSB interacts with many other proteins involved in DNA metabolism, with 22 such SSB-interacting proteins, or SIPs, defined to date. These interactions chiefly involve the disordered and conserved C-terminal residues of SSB. When not bound to ssDNA, SSB can aggregate to form a phase-separated biomolecular condensate. Current understanding of the properties of SSB and the functional significance of its many intermolecular interactions are summarized in this review.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"99-127"},"PeriodicalIF":6.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-01Epub Date: 2024-03-07DOI: 10.1080/10409238.2024.2318547
Philipp Schnee, Jürgen Pleiss, Albert Jeltsch
Protein lysine methyltransferases (PKMTs) transfer up to three methyl groups to the side chains of lysine residues in proteins and fulfill important regulatory functions by controlling protein stability, localization and protein/protein interactions. The methylation reactions are highly regulated, and aberrant methylation of proteins is associated with several types of diseases including neurologic disorders, cardiovascular diseases, and various types of cancer. This review describes novel insights into the catalytic machinery of various PKMTs achieved by the combined application of biochemical experiments and simulation approaches during the last years, focusing on clinically relevant and well-studied enzymes of this group like DOT1L, SMYD1-3, SET7/9, G9a/GLP, SETD2, SUV420H2, NSD1/2, different MLLs and EZH2. Biochemical experiments have unraveled many mechanistic features of PKMTs concerning their substrate and product specificity, processivity and the effects of somatic mutations observed in PKMTs in cancer cells. Structural data additionally provided information about the substrate recognition, enzyme-substrate complex formation, and allowed for simulations of the substrate peptide interaction and mechanism of PKMTs with atomistic resolution by molecular dynamics and hybrid quantum mechanics/molecular mechanics methods. These simulation technologies uncovered important mechanistic details of the PKMT reaction mechanism including the processes responsible for the deprotonation of the target lysine residue, essential conformational changes of the PKMT upon substrate binding, but also rationalized regulatory principles like PKMT autoinhibition. Further developments are discussed that could bring us closer to a mechanistic understanding of catalysis of this important class of enzymes in the near future. The results described here illustrate the power of the investigation of enzyme mechanisms by the combined application of biochemical experiments and simulation technologies.
{"title":"Approaching the catalytic mechanism of protein lysine methyltransferases by biochemical and simulation techniques.","authors":"Philipp Schnee, Jürgen Pleiss, Albert Jeltsch","doi":"10.1080/10409238.2024.2318547","DOIUrl":"10.1080/10409238.2024.2318547","url":null,"abstract":"<p><p>Protein lysine methyltransferases (PKMTs) transfer up to three methyl groups to the side chains of lysine residues in proteins and fulfill important regulatory functions by controlling protein stability, localization and protein/protein interactions. The methylation reactions are highly regulated, and aberrant methylation of proteins is associated with several types of diseases including neurologic disorders, cardiovascular diseases, and various types of cancer. This review describes novel insights into the catalytic machinery of various PKMTs achieved by the combined application of biochemical experiments and simulation approaches during the last years, focusing on clinically relevant and well-studied enzymes of this group like DOT1L, SMYD1-3, SET7/9, G9a/GLP, SETD2, SUV420H2, NSD1/2, different MLLs and EZH2. Biochemical experiments have unraveled many mechanistic features of PKMTs concerning their substrate and product specificity, processivity and the effects of somatic mutations observed in PKMTs in cancer cells. Structural data additionally provided information about the substrate recognition, enzyme-substrate complex formation, and allowed for simulations of the substrate peptide interaction and mechanism of PKMTs with atomistic resolution by molecular dynamics and hybrid quantum mechanics/molecular mechanics methods. These simulation technologies uncovered important mechanistic details of the PKMT reaction mechanism including the processes responsible for the deprotonation of the target lysine residue, essential conformational changes of the PKMT upon substrate binding, but also rationalized regulatory principles like PKMT autoinhibition. Further developments are discussed that could bring us closer to a mechanistic understanding of catalysis of this important class of enzymes in the near future. The results described here illustrate the power of the investigation of enzyme mechanisms by the combined application of biochemical experiments and simulation technologies.</p>","PeriodicalId":10794,"journal":{"name":"Critical Reviews in Biochemistry and Molecular Biology","volume":" ","pages":"20-68"},"PeriodicalIF":6.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}