Pub Date : 2024-07-01DOI: 10.1016/j.tibs.2024.03.013
Ludovic Autin , David S. Goodsell , Ivan Viola , Arthur Olson
In January 2024, a targeted conference, ‘CellVis2’, was held at Scripps Research in La Jolla, USA, the second in a series designed to explore the promise, practices, roadblocks, and prospects of creating, visualizing, sharing, and communicating physical representations of entire biological cells at scales down to the atom.
{"title":"CellVis2: a conference on visualizing the molecular cell","authors":"Ludovic Autin , David S. Goodsell , Ivan Viola , Arthur Olson","doi":"10.1016/j.tibs.2024.03.013","DOIUrl":"10.1016/j.tibs.2024.03.013","url":null,"abstract":"<div><p>In January 2024, a targeted conference, ‘CellVis2’, was held at Scripps Research in La Jolla, USA, the second in a series designed to explore the promise, practices, roadblocks, and prospects of creating, visualizing, sharing, and communicating physical representations of entire biological cells at scales down to the atom.</p></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":null,"pages":null},"PeriodicalIF":11.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140785273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/j.tibs.2024.05.002
Oren Shatz , Zvulun Elazar
Autophagy sequesters cytoplasmic portions into autophagosomes. While selective cargo is engulfed by elongation of cup-shaped isolation membranes (IMs), the morphogenesis of non-selective IMs remains elusive. Based on recent observations, we propose a novel model for autophagosome morphogenesis wherein active regulation of the IM rim serves the physiological roles of autophagy.
自噬将细胞质部分封存到自噬体中。选择性货物通过杯状隔离膜(IMs)的伸长被吞噬,而非选择性IMs的形态发生仍然难以捉摸。根据最近的观察结果,我们提出了一种新的自噬体形态发生模型,其中对 IM 边缘的主动调控为自噬的生理作用服务。
{"title":"The physiological relevance of autophagosome morphogenesis","authors":"Oren Shatz , Zvulun Elazar","doi":"10.1016/j.tibs.2024.05.002","DOIUrl":"10.1016/j.tibs.2024.05.002","url":null,"abstract":"<div><p>Autophagy sequesters cytoplasmic portions into autophagosomes. While selective cargo is engulfed by elongation of cup-shaped isolation membranes (IMs), the morphogenesis of non-selective IMs remains elusive. Based on recent observations, we propose a novel model for autophagosome morphogenesis wherein active regulation of the IM rim serves the physiological roles of autophagy.</p></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":null,"pages":null},"PeriodicalIF":11.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141140388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/j.tibs.2024.04.009
Rae M. Robertson-Anderson
{"title":"Optical tweezers microrheology maps micro-mechanics of complex systems","authors":"Rae M. Robertson-Anderson","doi":"10.1016/j.tibs.2024.04.009","DOIUrl":"10.1016/j.tibs.2024.04.009","url":null,"abstract":"","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":null,"pages":null},"PeriodicalIF":11.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141085893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/j.tibs.2024.03.014
Anton Maraldo , Jelena Rnjak-Kovacina , Christopher Marquis
Protein self-assembly, guided by the interplay of sequence- and environment-dependent liquid–liquid phase separation (LLPS), constitutes a fundamental process in the assembly of numerous intrinsically disordered proteins. Heuristic examination of these proteins has underscored the role of tyrosine residues, evident in their conservation and pivotal involvement in initiating LLPS and subsequent liquid–solid phase transitions (LSPT). The development of tyrosine-templated constructs, designed to mimic their natural counterparts, emerges as a promising strategy for creating adaptive, self-assembling systems with diverse applications. This review explores the central role of tyrosine in orchestrating protein self-assembly, delving into key interactions and examining its potential in innovative applications, including responsive biomaterials and bioengineering.
{"title":"Tyrosine – a structural glue for hierarchical protein assembly","authors":"Anton Maraldo , Jelena Rnjak-Kovacina , Christopher Marquis","doi":"10.1016/j.tibs.2024.03.014","DOIUrl":"10.1016/j.tibs.2024.03.014","url":null,"abstract":"<div><p>Protein self-assembly, guided by the interplay of sequence- and environment-dependent liquid–liquid phase separation (LLPS), constitutes a fundamental process in the assembly of numerous intrinsically disordered proteins. Heuristic examination of these proteins has underscored the role of tyrosine residues, evident in their conservation and pivotal involvement in initiating LLPS and subsequent liquid–solid phase transitions (LSPT). The development of tyrosine-templated constructs, designed to mimic their natural counterparts, emerges as a promising strategy for creating adaptive, self-assembling systems with diverse applications. This review explores the central role of tyrosine in orchestrating protein self-assembly, delving into key interactions and examining its potential in innovative applications, including responsive biomaterials and bioengineering.</p></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":null,"pages":null},"PeriodicalIF":11.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140775555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/S0968-0004(24)00142-7
{"title":"Subscription and Copyright Information","authors":"","doi":"10.1016/S0968-0004(24)00142-7","DOIUrl":"https://doi.org/10.1016/S0968-0004(24)00142-7","url":null,"abstract":"","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":null,"pages":null},"PeriodicalIF":11.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141595422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1016/j.tibs.2024.03.012
Irene Beusch , Hiten D. Madhani
The spliceosome catalyzes the splicing of pre-mRNAs. Although the spliceosome evolved from a prokaryotic self-splicing intron and an associated protein, it is a vastly more complex and dynamic ribonucleoprotein (RNP) whose function requires at least eight ATPases and multiple RNA rearrangements. These features afford stepwise opportunities for multiple inspections of the intron substrate, coupled with spliceosome disassembly for substrates that fail inspection. Early work using splicing-defective pre-mRNAs or small nuclear (sn)RNAs in Saccharomyces cerevisiae demonstrated that such checks could occur in catalytically active spliceosomes. We review recent results on pre-mRNA splicing in various systems, including humans, suggesting that earlier steps in spliceosome assembly are also subject to such quality control. The inspection–rejection framework helps explain the dynamic nature of the spliceosome.
剪接体催化前 mRNA 的剪接。虽然剪接体是由原核生物自我剪接的内含子和相关蛋白进化而来,但它是一种更为复杂和动态的核糖核蛋白(RNP),其功能至少需要八种 ATP 酶和多种 RNA 重排。这些特点为内含子底物的多次检测提供了逐步进行的机会,同时也为检测失败的底物提供了剪接体分解的机会。早期在酿酒酵母(Saccharomyces cerevisiae)中使用剪接缺陷前mRNA或小核糖核酸(sn)的研究表明,这种检查可以在催化活性剪接体中发生。我们回顾了包括人类在内的各种系统中前 mRNA 剪接的最新结果,表明剪接体组装的早期步骤也会受到这种质量控制的影响。检查-排斥框架有助于解释剪接体的动态性质。
{"title":"Understanding the dynamic design of the spliceosome","authors":"Irene Beusch , Hiten D. Madhani","doi":"10.1016/j.tibs.2024.03.012","DOIUrl":"10.1016/j.tibs.2024.03.012","url":null,"abstract":"<div><p>The spliceosome catalyzes the splicing of pre-mRNAs. Although the spliceosome evolved from a prokaryotic self-splicing intron and an associated protein, it is a vastly more complex and dynamic ribonucleoprotein (RNP) whose function requires at least eight ATPases and multiple RNA rearrangements. These features afford stepwise opportunities for multiple inspections of the intron substrate, coupled with spliceosome disassembly for substrates that fail inspection. Early work using splicing-defective pre-mRNAs or small nuclear (sn)RNAs in <em>Saccharomyces cerevisiae</em> demonstrated that such checks could occur in catalytically active spliceosomes. We review recent results on pre-mRNA splicing in various systems, including humans, suggesting that earlier steps in spliceosome assembly are also subject to such quality control. The inspection–rejection framework helps explain the dynamic nature of the spliceosome.</p></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":null,"pages":null},"PeriodicalIF":11.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0968000424000781/pdfft?md5=bbb6aeb7e63838ff600a8cb1ff1d8071&pid=1-s2.0-S0968000424000781-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140776366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 : 2024-07-01DOI: 10.1016/S0968-0004(24)00139-7
{"title":"Advisory Board and Contents","authors":"","doi":"10.1016/S0968-0004(24)00139-7","DOIUrl":"https://doi.org/10.1016/S0968-0004(24)00139-7","url":null,"abstract":"","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":null,"pages":null},"PeriodicalIF":11.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0968000424001397/pdfft?md5=f6dd74a40dda1b1e9174b0f103373d8c&pid=1-s2.0-S0968000424001397-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141595513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 : 2024-06-01DOI: 10.1016/j.tibs.2024.03.006
Emmanuel Flores-Espinoza , Alex R.B. Thomsen
G protein-coupled receptors (GPCRs) located at the cell surface bind extracellular ligands and convey intracellular signals via activation of heterotrimeric G proteins. Traditionally, G protein signaling was viewed to occur exclusively at this subcellular region followed by rapid desensitization facilitated by β-arrestin (βarr)-mediated G protein uncoupling and receptor internalization. However, emerging evidence over the past 15 years suggests that these βarr-mediated events do not necessarily terminate receptor signaling and that some GPCRs continue to activate G proteins after having been internalized into endosomes. Here, we review the recently elucidated mechanistic basis underlying endosomal GPCR signaling and discuss physiological implications and pharmacological targeting of this newly appreciated signaling mode.
位于细胞表面的 G 蛋白偶联受体(GPCR)与细胞外配体结合,并通过激活异三聚 G 蛋白传递细胞内信号。传统观点认为,G 蛋白信号传导只发生在这一亚细胞区域,随后在 β-阻遏素(βarr)介导的 G 蛋白解偶联和受体内化作用下迅速脱敏。然而,过去 15 年中新出现的证据表明,这些由 βarr 介导的事件并不一定会终止受体信号传导,一些 GPCR 在内化到内体后仍会继续激活 G 蛋白。在此,我们回顾了最近阐明的内泌体 GPCR 信号转导的机理基础,并讨论了这种新近受到重视的信号转导模式的生理意义和药理作用。
{"title":"Beneath the surface: endosomal GPCR signaling","authors":"Emmanuel Flores-Espinoza , Alex R.B. Thomsen","doi":"10.1016/j.tibs.2024.03.006","DOIUrl":"10.1016/j.tibs.2024.03.006","url":null,"abstract":"<div><p>G protein-coupled receptors (GPCRs) located at the cell surface bind extracellular ligands and convey intracellular signals via activation of heterotrimeric G proteins. Traditionally, G protein signaling was viewed to occur exclusively at this subcellular region followed by rapid desensitization facilitated by β-arrestin (βarr)-mediated G protein uncoupling and receptor internalization. However, emerging evidence over the past 15 years suggests that these βarr-mediated events do not necessarily terminate receptor signaling and that some GPCRs continue to activate G proteins after having been internalized into endosomes. Here, we review the recently elucidated mechanistic basis underlying endosomal GPCR signaling and discuss physiological implications and pharmacological targeting of this newly appreciated signaling mode.</p></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140760577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.tibs.2024.03.007
Monica Perri , Francesco Licausi
Thiol oxidation to dioxygenated sulfinic acid is catalyzed by an enzyme family characterized by a cupin fold. These proteins act on free thiol-containing molecules to generate central metabolism precursors and signaling compounds in bacteria, fungi, and animal cells. In plants and animals, they also oxidize exposed N-cysteinyl residues, directing proteins to proteolysis. Enzyme kinetics, X-ray crystallography, and spectroscopy studies prompted the formulation and testing of hypotheses about the mechanism of action and the different substrate specificity of these enzymes. Concomitantly, the physiological role of thiol dioxygenation in prokaryotes and eukaryotes has been studied through genetic and physiological approaches. Further structural characterization is necessary to enable precise and safe manipulation of thiol dioxygenases (TDOs) for therapeutic, industrial, and agricultural applications.
{"title":"Thiol dioxygenases: from structures to functions","authors":"Monica Perri , Francesco Licausi","doi":"10.1016/j.tibs.2024.03.007","DOIUrl":"10.1016/j.tibs.2024.03.007","url":null,"abstract":"<div><p>Thiol oxidation to dioxygenated sulfinic acid is catalyzed by an enzyme family characterized by a cupin fold. These proteins act on free thiol-containing molecules to generate central metabolism precursors and signaling compounds in bacteria, fungi, and animal cells. In plants and animals, they also oxidize exposed N-cysteinyl residues, directing proteins to proteolysis. Enzyme kinetics, X-ray crystallography, and spectroscopy studies prompted the formulation and testing of hypotheses about the mechanism of action and the different substrate specificity of these enzymes. Concomitantly, the physiological role of thiol dioxygenation in prokaryotes and eukaryotes has been studied through genetic and physiological approaches. Further structural characterization is necessary to enable precise and safe manipulation of thiol dioxygenases (TDOs) for therapeutic, industrial, and agricultural applications.</p></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0968000424000732/pdfft?md5=c3a169ce954c4a136b6d347c6f9b1923&pid=1-s2.0-S0968000424000732-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140789320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 : 2024-06-01DOI: 10.1016/j.tibs.2024.03.004
Bo Wang , Gautam Pareek , Mondira Kundu
Autophagy – a highly regulated intracellular degradation process – is pivotal in maintaining cellular homeostasis. Liquid–liquid phase separation (LLPS) is a fundamental mechanism regulating the formation and function of membrane-less compartments. Recent research has unveiled connections between LLPS and autophagy, suggesting that phase separation events may orchestrate the spatiotemporal organization of autophagic machinery and cargo sequestration. The Unc-51-like kinase (ULK)/autophagy-related 1 (Atg1) family of proteins is best known for its regulatory role in initiating autophagy, but there is growing evidence that the functional spectrum of ULK/Atg1 extends beyond autophagy regulation. In this review, we explore the spatial and temporal regulation of the ULK/Atg1 family of kinases, focusing on their recruitment to LLPS-driven compartments, and highlighting their multifaceted functions beyond their traditional role.
{"title":"ULK/Atg1: phasing in and out of autophagy","authors":"Bo Wang , Gautam Pareek , Mondira Kundu","doi":"10.1016/j.tibs.2024.03.004","DOIUrl":"10.1016/j.tibs.2024.03.004","url":null,"abstract":"<div><p>Autophagy – a highly regulated intracellular degradation process – is pivotal in maintaining cellular homeostasis. Liquid–liquid phase separation (LLPS) is a fundamental mechanism regulating the formation and function of membrane-less compartments. Recent research has unveiled connections between LLPS and autophagy, suggesting that phase separation events may orchestrate the spatiotemporal organization of autophagic machinery and cargo sequestration. The Unc-51-like kinase (ULK)/autophagy-related 1 (Atg1) family of proteins is best known for its regulatory role in initiating autophagy, but there is growing evidence that the functional spectrum of ULK/Atg1 extends beyond autophagy regulation. In this review, we explore the spatial and temporal regulation of the ULK/Atg1 family of kinases, focusing on their recruitment to LLPS-driven compartments, and highlighting their multifaceted functions beyond their traditional role.</p></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140761128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}