Pub Date : 2023-06-20Epub Date: 2023-03-31DOI: 10.1146/annurev-biochem-052521-040313
Christian Siebold, Rajat Rohatgi
Ligands of the Hedgehog (HH) pathway are paracrine signaling molecules that coordinate tissue development in metazoans. A remarkable feature of HH signaling is the repeated use of cholesterol in steps spanning ligand biogenesis, secretion, dispersal, and reception on target cells. A cholesterol molecule covalently attached to HH ligands is used as a molecular baton by transfer proteins to guide their secretion, spread, and reception. On target cells, a signaling circuit composed of a cholesterol transporter and sensor regulates transmission of HH signals across the plasma membrane to the cytoplasm. The repeated use of cholesterol in signaling supports the view that the HH pathway likely evolved by coopting ancient systems to regulate the abundance or organization of sterol-like lipids in membranes.
{"title":"The Inseparable Relationship Between Cholesterol and Hedgehog Signaling.","authors":"Christian Siebold, Rajat Rohatgi","doi":"10.1146/annurev-biochem-052521-040313","DOIUrl":"10.1146/annurev-biochem-052521-040313","url":null,"abstract":"<p><p>Ligands of the Hedgehog (HH) pathway are paracrine signaling molecules that coordinate tissue development in metazoans. A remarkable feature of HH signaling is the repeated use of cholesterol in steps spanning ligand biogenesis, secretion, dispersal, and reception on target cells. A cholesterol molecule covalently attached to HH ligands is used as a molecular baton by transfer proteins to guide their secretion, spread, and reception. On target cells, a signaling circuit composed of a cholesterol transporter and sensor regulates transmission of HH signals across the plasma membrane to the cytoplasm. The repeated use of cholesterol in signaling supports the view that the HH pathway likely evolved by coopting ancient systems to regulate the abundance or organization of sterol-like lipids in membranes.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"92 ","pages":"273-298"},"PeriodicalIF":12.1,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10330520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9769873","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 : 2023-06-20DOI: 10.1146/annurev-biochem-052521-033250
Eunhee Choi, Xiao-Chen Bai
The insulin receptor (IR) is a type II receptor tyrosine kinase that plays essential roles in metabolism, growth, and proliferation. Dysregulation of IR signaling is linked to many human diseases, such as diabetes and cancers. The resolution revolution in cryo-electron microscopy has led to the determination of several structures of IR with different numbers of bound insulin molecules in recent years, which have tremendously improved our understanding of how IR is activated by insulin. Here, we review the insulin-induced activation mechanism of IR, including (a) the detailed binding modes and functions of insulin at site 1 and site 2 and (b) the insulin-induced structural transitions that are required for IR activation. We highlight several other key aspects of the activation and regulation of IR signaling and discuss the remaining gaps in our understanding of the IR activation mechanism and potential avenues of future research.
{"title":"The Activation Mechanism of the Insulin Receptor: A Structural Perspective.","authors":"Eunhee Choi, Xiao-Chen Bai","doi":"10.1146/annurev-biochem-052521-033250","DOIUrl":"https://doi.org/10.1146/annurev-biochem-052521-033250","url":null,"abstract":"<p><p>The insulin receptor (IR) is a type II receptor tyrosine kinase that plays essential roles in metabolism, growth, and proliferation. Dysregulation of IR signaling is linked to many human diseases, such as diabetes and cancers. The resolution revolution in cryo-electron microscopy has led to the determination of several structures of IR with different numbers of bound insulin molecules in recent years, which have tremendously improved our understanding of how IR is activated by insulin. Here, we review the insulin-induced activation mechanism of IR, including (<i>a</i>) the detailed binding modes and functions of insulin at site 1 and site 2 and (<i>b</i>) the insulin-induced structural transitions that are required for IR activation. We highlight several other key aspects of the activation and regulation of IR signaling and discuss the remaining gaps in our understanding of the IR activation mechanism and potential avenues of future research.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"92 ","pages":"247-272"},"PeriodicalIF":16.6,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10398885/pdf/nihms-1919378.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9929688","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 : 2023-06-20DOI: 10.1146/annurev-biochem-052521-035330
Mathieu N Flamand, Matthew Tegowski, Kate D Meyer
Over the past decade, mRNA modifications have emerged as important regulators of gene expression control in cells. Fueled in large part by the development of tools for detecting RNA modifications transcriptome wide, researchers have uncovered a diverse epitranscriptome that serves as an additional layer of gene regulation beyond simple RNA sequence. Here, we review the proteins that write, read, and erase these marks, with a particular focus on the most abundant internal modification, N6-methyladenosine (m6A). We first describe the discovery of the key enzymes that deposit and remove m6A and other modifications and discuss how our understanding of these proteins has shaped our views of modification dynamics. We then review current models for the function of m6A reader proteins and how our knowledge of these proteins has evolved. Finally, we highlight important future directions for the field and discuss key questions that remain unanswered.
{"title":"The Proteins of mRNA Modification: Writers, Readers, and Erasers.","authors":"Mathieu N Flamand, Matthew Tegowski, Kate D Meyer","doi":"10.1146/annurev-biochem-052521-035330","DOIUrl":"https://doi.org/10.1146/annurev-biochem-052521-035330","url":null,"abstract":"<p><p>Over the past decade, mRNA modifications have emerged as important regulators of gene expression control in cells. Fueled in large part by the development of tools for detecting RNA modifications transcriptome wide, researchers have uncovered a diverse epitranscriptome that serves as an additional layer of gene regulation beyond simple RNA sequence. Here, we review the proteins that write, read, and erase these marks, with a particular focus on the most abundant internal modification, <i>N</i><sup>6</sup>-methyladenosine (m<sup>6</sup>A). We first describe the discovery of the key enzymes that deposit and remove m<sup>6</sup>A and other modifications and discuss how our understanding of these proteins has shaped our views of modification dynamics. We then review current models for the function of m<sup>6</sup>A reader proteins and how our knowledge of these proteins has evolved. Finally, we highlight important future directions for the field and discuss key questions that remain unanswered.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"92 ","pages":"145-173"},"PeriodicalIF":16.6,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443600/pdf/nihms-1922506.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10042992","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 : 2023-06-20DOI: 10.1146/annurev-biochem-071322-021330
Stephanie Vrijsen, Marine Houdou, Ana Cascalho, Jan Eggermont, Peter Vangheluwe
The polyamines putrescine, spermidine, and spermine are abundant polycations of vital importance in mammalian cells. Their cellular levels are tightly regulated by degradation and synthesis, as well as by uptake and export. Here, we discuss the delicate balance between the neuroprotective and neurotoxic effects of polyamines in the context of Parkinson's disease (PD). Polyamine levels decline with aging and are altered in patients with PD, whereas recent mechanistic studies on ATP13A2 (PARK9) demonstrated a driving role of a disturbed polyamine homeostasis in PD. Polyamines affect pathways in PD pathogenesis, such as α-synuclein aggregation, and influence PD-related processes like autophagy, heavy metal toxicity, oxidative stress, neuroinflammation, and lysosomal/mitochondrial dysfunction. We formulate outstanding research questions regarding the role of polyamines in PD, their potential as PD biomarkers, and possible therapeutic strategies for PD targeting polyamine homeostasis.
{"title":"Polyamines in Parkinson's Disease: Balancing Between Neurotoxicity and Neuroprotection.","authors":"Stephanie Vrijsen, Marine Houdou, Ana Cascalho, Jan Eggermont, Peter Vangheluwe","doi":"10.1146/annurev-biochem-071322-021330","DOIUrl":"https://doi.org/10.1146/annurev-biochem-071322-021330","url":null,"abstract":"<p><p>The polyamines putrescine, spermidine, and spermine are abundant polycations of vital importance in mammalian cells. Their cellular levels are tightly regulated by degradation and synthesis, as well as by uptake and export. Here, we discuss the delicate balance between the neuroprotective and neurotoxic effects of polyamines in the context of Parkinson's disease (PD). Polyamine levels decline with aging and are altered in patients with PD, whereas recent mechanistic studies on ATP13A2 (PARK9) demonstrated a driving role of a disturbed polyamine homeostasis in PD. Polyamines affect pathways in PD pathogenesis, such as α-synuclein aggregation, and influence PD-related processes like autophagy, heavy metal toxicity, oxidative stress, neuroinflammation, and lysosomal/mitochondrial dysfunction. We formulate outstanding research questions regarding the role of polyamines in PD, their potential as PD biomarkers, and possible therapeutic strategies for PD targeting polyamine homeostasis.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"92 ","pages":"435-464"},"PeriodicalIF":16.6,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9662523","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 : 2023-06-20Epub Date: 2023-03-31DOI: 10.1146/annurev-biochem-052621-091808
Qiushuang Wu, Ariel A Bazzini
Messenger RNA (mRNA) stability and translational efficiency are two crucial aspects of the post-transcriptional process that profoundly impact protein production in a cell. While it is widely known that ribosomes produce proteins, studies during the past decade have surprisingly revealed that ribosomes also control mRNA stability in a codon-dependent manner, a process referred to as codon optimality. Therefore, codons, the three-nucleotide words read by the ribosome, have a potent effect on mRNA stability and provide cis-regulatory information that extends beyond the amino acids they encode. While the codon optimality molecular mechanism is still unclear, the translation elongation rate appears to trigger mRNA decay. Thus, transfer RNAs emerge as potential master gene regulators affecting mRNA stability. Furthermore, while few factors related to codon optimality have been identified in yeast, the orthologous genes in vertebrates do not necessary share the same functions. Here, we discuss codon optimality findings and gene regulation layers related to codon composition in different eukaryotic species.
{"title":"Translation and mRNA Stability Control.","authors":"Qiushuang Wu, Ariel A Bazzini","doi":"10.1146/annurev-biochem-052621-091808","DOIUrl":"10.1146/annurev-biochem-052621-091808","url":null,"abstract":"<p><p>Messenger RNA (mRNA) stability and translational efficiency are two crucial aspects of the post-transcriptional process that profoundly impact protein production in a cell. While it is widely known that ribosomes produce proteins, studies during the past decade have surprisingly revealed that ribosomes also control mRNA stability in a codon-dependent manner, a process referred to as codon optimality. Therefore, codons, the three-nucleotide words read by the ribosome, have a potent effect on mRNA stability and provide cis<i>-</i>regulatory information that extends beyond the amino acids they encode. While the codon optimality molecular mechanism is still unclear, the translation elongation rate appears to trigger mRNA decay. Thus, transfer RNAs emerge as potential master gene regulators affecting mRNA stability. Furthermore, while few factors related to codon optimality have been identified in yeast, the orthologous genes in vertebrates do not necessary share the same functions. Here, we discuss codon optimality findings and gene regulation layers related to codon composition in different eukaryotic species.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"92 ","pages":"227-245"},"PeriodicalIF":12.1,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9668847","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 : 2022-06-21Epub Date: 2022-03-18DOI: 10.1146/annurev-biochem-032620-104508
Kami Ahmad, Steven Henikoff, Srinivas Ramachandran
Gene regulation arises out of dynamic competition between nucleosomes, transcription factors, and other chromatin proteins for the opportunity to bind genomic DNA. The timescales of nucleosome assembly and binding of factors to DNA determine the outcomes of this competition at any given locus. Here, we review how these properties of chromatin proteins and the interplay between the dynamics of different factors are critical for gene regulation. We discuss how molecular structures of large chromatin-associated complexes, kinetic measurements, and high resolution mapping of protein-DNA complexes in vivo set the boundary conditions for chromatin dynamics, leading to models of how the steady state behaviors of regulatory elements arise.
基因调控源于核小体、转录因子和其他染色质蛋白之间为争夺与基因组 DNA 结合的机会而展开的动态竞争。核小体组装和因子与 DNA 结合的时间尺度决定了任何给定基因座上这种竞争的结果。在这里,我们将回顾染色质蛋白的这些特性以及不同因子动态之间的相互作用是如何对基因调控起到关键作用的。我们将讨论大型染色质相关复合物的分子结构、动力学测量以及体内蛋白质-DNA 复合物的高分辨率图谱如何为染色质动力学设定边界条件,从而建立调控因子稳态行为的模型。
{"title":"Managing the Steady State Chromatin Landscape by Nucleosome Dynamics.","authors":"Kami Ahmad, Steven Henikoff, Srinivas Ramachandran","doi":"10.1146/annurev-biochem-032620-104508","DOIUrl":"10.1146/annurev-biochem-032620-104508","url":null,"abstract":"<p><p>Gene regulation arises out of dynamic competition between nucleosomes, transcription factors, and other chromatin proteins for the opportunity to bind genomic DNA. The timescales of nucleosome assembly and binding of factors to DNA determine the outcomes of this competition at any given locus. Here, we review how these properties of chromatin proteins and the interplay between the dynamics of different factors are critical for gene regulation. We discuss how molecular structures of large chromatin-associated complexes, kinetic measurements, and high resolution mapping of protein-DNA complexes in vivo set the boundary conditions for chromatin dynamics, leading to models of how the steady state behaviors of regulatory elements arise.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"91 ","pages":"183-195"},"PeriodicalIF":12.1,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10277172/pdf/nihms-1814593.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10019043","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 : 2022-06-21DOI: 10.1146/annurev-biochem-040320-105145
Alvin C Y Kuk, Aili Hao, Seok-Yong Lee
Biosynthesis of many important polysaccharides (including peptidoglycan, lipopolysaccharide, and N-linked glycans) necessitates the transport of lipid-linked oligosaccharides (LLO) across membranes from their cytosolic site of synthesis to their sites of utilization. Much of our current understanding of LLO transport comes from genetic, biochemical, and structural studies of the multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) superfamily protein MurJ, which flips the peptidoglycan precursor lipid II. MurJ plays a pivotal role in bacterial cell wall synthesis and is an emerging antibiotic target. Here, we review the mechanism of LLO flipping by MurJ, including the structural basis for lipid II flipping and ion coupling. We then discuss inhibition of MurJ by antibacterials, including humimycins and the phage M lysis protein, as well as how studies on MurJ could provide insight into other flippases, both within and beyond the MOP superfamily.
{"title":"Structure and Mechanism of the Lipid Flippase MurJ.","authors":"Alvin C Y Kuk, Aili Hao, Seok-Yong Lee","doi":"10.1146/annurev-biochem-040320-105145","DOIUrl":"https://doi.org/10.1146/annurev-biochem-040320-105145","url":null,"abstract":"<p><p>Biosynthesis of many important polysaccharides (including peptidoglycan, lipopolysaccharide, and <i>N</i>-linked glycans) necessitates the transport of lipid-linked oligosaccharides (LLO) across membranes from their cytosolic site of synthesis to their sites of utilization. Much of our current understanding of LLO transport comes from genetic, biochemical, and structural studies of the multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) superfamily protein MurJ, which flips the peptidoglycan precursor lipid II. MurJ plays a pivotal role in bacterial cell wall synthesis and is an emerging antibiotic target. Here, we review the mechanism of LLO flipping by MurJ, including the structural basis for lipid II flipping and ion coupling. We then discuss inhibition of MurJ by antibacterials, including humimycins and the phage M lysis protein, as well as how studies on MurJ could provide insight into other flippases, both within and beyond the MOP superfamily.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"91 ","pages":"705-729"},"PeriodicalIF":16.6,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10108830/pdf/nihms-1871783.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9701467","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 : 2022-06-21Epub Date: 2022-03-14DOI: 10.1146/annurev-biochem-032620-105738
Melinda M Diver, John V Lin King, David Julius, Yifan Cheng
Transient receptor potential (TRP) ion channels are sophisticated signaling machines that detect a wide variety of environmental and physiological signals. Every cell in the body expresses one or more members of the extended TRP channel family, which consists of over 30 subtypes, each likely possessing distinct pharmacological, biophysical, and/or structural attributes. While the function of some TRP subtypes remains enigmatic, those involved in sensory signaling are perhaps best characterized and have served as models for understanding how these excitatory ion channels serve as polymodal signal integrators. With the recent resolution revolution in cryo-electron microscopy, these and other TRP channel subtypes are now yielding their secrets to detailed atomic analysis, which is beginning to reveal structural underpinnings of stimulus detection and gating, ion permeation, and allosteric mechanisms governing signal integration. These insights are providing a framework for designing and evaluating modality-specific pharmacological agents for treating sensory and other TRP channel-associated disorders.
{"title":"Sensory TRP Channels in Three Dimensions.","authors":"Melinda M Diver, John V Lin King, David Julius, Yifan Cheng","doi":"10.1146/annurev-biochem-032620-105738","DOIUrl":"10.1146/annurev-biochem-032620-105738","url":null,"abstract":"<p><p>Transient receptor potential (TRP) ion channels are sophisticated signaling machines that detect a wide variety of environmental and physiological signals. Every cell in the body expresses one or more members of the extended TRP channel family, which consists of over 30 subtypes, each likely possessing distinct pharmacological, biophysical, and/or structural attributes. While the function of some TRP subtypes remains enigmatic, those involved in sensory signaling are perhaps best characterized and have served as models for understanding how these excitatory ion channels serve as polymodal signal integrators. With the recent resolution revolution in cryo-electron microscopy, these and other TRP channel subtypes are now yielding their secrets to detailed atomic analysis, which is beginning to reveal structural underpinnings of stimulus detection and gating, ion permeation, and allosteric mechanisms governing signal integration. These insights are providing a framework for designing and evaluating modality-specific pharmacological agents for treating sensory and other TRP channel-associated disorders.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"91 ","pages":"629-649"},"PeriodicalIF":12.1,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233036/pdf/nihms-1809634.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9702300","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 : 2022-06-21DOI: 10.1146/annurev-biochem-032620-105728
Anthony M Pedley, Vidhi Pareek, Stephen J Benkovic
Over the past fifteen years, we have unveiled a new mechanism by which cells achieve greater efficiency in de novo purine biosynthesis. This mechanism relies on the compartmentalization of de novo purine biosynthetic enzymes into a dynamic complex called the purinosome. In this review, we highlight our current understanding of the purinosome with emphasis on its biophysical properties and function and on the cellular mechanisms that regulate its assembly. We propose a model for functional purinosomes in which they consist of at least ten enzymes that localize near mitochondria and carry out de novo purine biosynthesis by metabolic channeling. We conclude by discussing challenges and opportunities associated with studying the purinosome and analogous metabolons.
{"title":"The Purinosome: A Case Study for a Mammalian Metabolon.","authors":"Anthony M Pedley, Vidhi Pareek, Stephen J Benkovic","doi":"10.1146/annurev-biochem-032620-105728","DOIUrl":"https://doi.org/10.1146/annurev-biochem-032620-105728","url":null,"abstract":"<p><p>Over the past fifteen years, we have unveiled a new mechanism by which cells achieve greater efficiency in de novo purine biosynthesis. This mechanism relies on the compartmentalization of de novo purine biosynthetic enzymes into a dynamic complex called the purinosome. In this review, we highlight our current understanding of the purinosome with emphasis on its biophysical properties and function and on the cellular mechanisms that regulate its assembly. We propose a model for functional purinosomes in which they consist of at least ten enzymes that localize near mitochondria and carry out de novo purine biosynthesis by metabolic channeling. We conclude by discussing challenges and opportunities associated with studying the purinosome and analogous metabolons.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"91 ","pages":"89-106"},"PeriodicalIF":16.6,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9531488/pdf/nihms-1837650.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9701464","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 : 2022-06-21DOI: 10.1146/annurev-biochem-032620-110705
Eugene Y D Chua, Joshua H Mendez, Micah Rapp, Serban L Ilca, Yong Zi Tan, Kashyap Maruthi, Huihui Kuang, Christina M Zimanyi, Anchi Cheng, Edward T Eng, Alex J Noble, Clinton S Potter, Bridget Carragher
Cryo-electron microscopy (cryo-EM) continues its remarkable growth as a method for visualizing biological objects, which has been driven by advances across the entire pipeline. Developments in both single-particle analysis and in situ tomography have enabled more structures to be imaged and determined to better resolutions, at faster speeds, and with more scientists having improved access. This review highlights recent advances at each stageof the cryo-EM pipeline and provides examples of how these techniques have been used to investigate real-world problems, including antibody development against the SARS-CoV-2 spike during the recent COVID-19 pandemic.
{"title":"Better, Faster, Cheaper: Recent Advances in Cryo-Electron Microscopy.","authors":"Eugene Y D Chua, Joshua H Mendez, Micah Rapp, Serban L Ilca, Yong Zi Tan, Kashyap Maruthi, Huihui Kuang, Christina M Zimanyi, Anchi Cheng, Edward T Eng, Alex J Noble, Clinton S Potter, Bridget Carragher","doi":"10.1146/annurev-biochem-032620-110705","DOIUrl":"https://doi.org/10.1146/annurev-biochem-032620-110705","url":null,"abstract":"<p><p>Cryo-electron microscopy (cryo-EM) continues its remarkable growth as a method for visualizing biological objects, which has been driven by advances across the entire pipeline. Developments in both single-particle analysis and in situ tomography have enabled more structures to be imaged and determined to better resolutions, at faster speeds, and with more scientists having improved access. This review highlights recent advances at each stageof the cryo-EM pipeline and provides examples of how these techniques have been used to investigate real-world problems, including antibody development against the SARS-CoV-2 spike during the recent COVID-19 pandemic.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"91 ","pages":"1-32"},"PeriodicalIF":16.6,"publicationDate":"2022-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393189/pdf/nihms-1916146.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286487","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}