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Taming AID mutator activity in somatic hypermutation 驯服体细胞超突变中的 AID 突变体活性
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2024-07-01 DOI: 10.1016/j.tibs.2024.03.011
Yining Qin , Fei-Long Meng
{"title":"Taming AID mutator activity in somatic hypermutation","authors":"Yining Qin ,&nbsp;Fei-Long Meng","doi":"10.1016/j.tibs.2024.03.011","DOIUrl":"10.1016/j.tibs.2024.03.011","url":null,"abstract":"<div><p>Activation-induced cytidine deaminase (AID) initiates somatic hypermutation (SHM) by introducing base substitutions into antibody genes, a process enabling antibody affinity maturation in immune response. How a mutator is tamed to precisely and safely generate programmed DNA lesions in a physiological process remains unsettled, as its dysregulation drives lymphomagenesis. Recent research has revealed several hidden features of AID-initiated mutagenesis: preferential activity on flexible DNA substrates, restrained activity within chromatin loop domains, unique DNA repair factors to differentially decode AID-caused lesions, and diverse consequences of aberrant deamination. Here, we depict the multifaceted regulation of AID activity with a focus on emerging concepts/factors and discuss their implications for the design of base editors (BEs) that install somatic mutations to correct deleterious genomic variants.</p></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"49 7","pages":"Pages 622-632"},"PeriodicalIF":11.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140782236","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}
引用次数: 0
Hypoxia research, where to now? 缺氧研究，何去何从？
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2024-07-01 DOI: 10.1016/j.tibs.2024.03.008
Brian M. Ortmann , Cormac T. Taylor , Sonia Rocha
{"title":"Hypoxia research, where to now?","authors":"Brian M. Ortmann ,&nbsp;Cormac T. Taylor ,&nbsp;Sonia Rocha","doi":"10.1016/j.tibs.2024.03.008","DOIUrl":"10.1016/j.tibs.2024.03.008","url":null,"abstract":"<div><p>Investigating how cells and organisms sense and respond to O<sub>2</sub> levels is essential to our understanding of physiology and pathology. This field has advanced considerably since the discovery of the major transcription factor family, hypoxia-inducible factor (HIF), and the enzymes that control its levels: prolyl hydroxylases (PHDs). However, with its expansion, new complexities have emerged. Herein we highlight three main areas where, in our opinion, the research community could direct some of their attention. These include non-transcriptional roles of HIFs, specificity and O<sub>2</sub> sensitivity of 2-oxoglutarate-dependent dioxygenases (2-OGDDs), and new tools and methods to detect O<sub>2</sub> concentrations in cells and organs. A greater understanding of these areas would answer big questions and help drive our knowledge of cellular responses to hypoxia forward.</p></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"49 7","pages":"Pages 573-582"},"PeriodicalIF":11.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0968000424000744/pdfft?md5=8af808306ecf659f964ebdb735e9e71f&pid=1-s2.0-S0968000424000744-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140769938","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}
引用次数: 0
Sortases: structure, mechanism, and implications for protein engineering 排序酶：结构、机制和对蛋白质工程的影响。
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2024-07-01 DOI: 10.1016/j.tibs.2024.04.003
Jeanine F. Amacher , John M. Antos
{"title":"Sortases: structure, mechanism, and implications for protein engineering","authors":"Jeanine F. Amacher ,&nbsp;John M. Antos","doi":"10.1016/j.tibs.2024.04.003","DOIUrl":"10.1016/j.tibs.2024.04.003","url":null,"abstract":"<div><p>Sortase enzymes are critical cysteine transpeptidases on the surface of bacteria that attach proteins to the cell wall and are involved in the construction of bacterial pili. Due to their ability to recognize specific substrates and covalently ligate a range of reaction partners, sortases are widely used in protein engineering applications via sortase-mediated ligation (SML) strategies. In this review, we discuss recent structural studies elucidating key aspects of sortase specificity and the catalytic mechanism. We also highlight select recent applications of SML, including examples where fundamental studies of sortase structure and function have informed the continued development of these enzymes as tools for protein engineering.</p></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"49 7","pages":"Pages 596-610"},"PeriodicalIF":11.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847985","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}
引用次数: 0
(G)Patching up mis-splicing in cancer (G）修补癌症中的错误拼接。
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2024-07-01 DOI: 10.1016/j.tibs.2024.05.001
Maciej Cieśla , Cristian Bellodi
{"title":"(G)Patching up mis-splicing in cancer","authors":"Maciej Cieśla ,&nbsp;Cristian Bellodi","doi":"10.1016/j.tibs.2024.05.001","DOIUrl":"10.1016/j.tibs.2024.05.001","url":null,"abstract":"<div><p><span>Benbarche, Pineda, Galvis, <em>et al</em></span><svg><path></path></svg>. delineate an essential role for the G-patch motif-containing protein GPATCH8 in mis-splicing associated with cancer-driving mutations of the splicing factor SF3B1. GPATCH8 cooperates with SF3B1 mutants, affecting the splicing machinery. Targeting GPATCH8 reveals therapeutic opportunities for SF3B1 mutant cancers and other splicing-related diseases.</p></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"49 7","pages":"Pages 564-566"},"PeriodicalIF":11.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0968000424001117/pdfft?md5=992ef460e36147ebeca6d8b384082ba2&pid=1-s2.0-S0968000424001117-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140954754","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}
引用次数: 0
The physiological relevance of autophagosome morphogenesis 自噬体形态发生的生理意义
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2024-07-01 DOI: 10.1016/j.tibs.2024.05.002
Oren Shatz , Zvulun Elazar
{"title":"The physiological relevance of autophagosome morphogenesis","authors":"Oren Shatz ,&nbsp;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":"49 7","pages":"Pages 569-572"},"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}
引用次数: 0
Subconductance states add complexity to Piezo1 gating model 亚导状态增加了 Piezo1 门控模型的复杂性。
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2024-07-01 DOI: 10.1016/j.tibs.2024.05.005
Marie E. Cronin , Jörg Grandl
{"title":"Subconductance states add complexity to Piezo1 gating model","authors":"Marie E. Cronin ,&nbsp;Jörg Grandl","doi":"10.1016/j.tibs.2024.05.005","DOIUrl":"10.1016/j.tibs.2024.05.005","url":null,"abstract":"<div><p>Piezos are force-gated ion channels that detect and communicate membrane tension to the cell. Recent work from <span>Ullah, Nosyreva</span><svg><path></path></svg>, and colleagues characterizes partial channel openings, known as subconductance states, and develops a new gating model of Piezo1 function.</p></div>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":"49 7","pages":"Pages 567-568"},"PeriodicalIF":11.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178353","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}
引用次数: 0
CellVis2: a conference on visualizing the molecular cell CellVis2：分子细胞可视化会议
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2024-07-01 DOI: 10.1016/j.tibs.2024.03.013
Ludovic Autin , David S. Goodsell , Ivan Viola , Arthur Olson
{"title":"CellVis2: a conference on visualizing the molecular cell","authors":"Ludovic Autin ,&nbsp;David S. Goodsell ,&nbsp;Ivan Viola ,&nbsp;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":"49 7","pages":"Pages 559-563"},"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}
引用次数: 0
Tyrosine – a structural glue for hierarchical protein assembly 酪氨酸--分层蛋白质组装的结构粘合剂。
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2024-07-01 DOI: 10.1016/j.tibs.2024.03.014
Anton Maraldo , Jelena Rnjak-Kovacina , Christopher Marquis
{"title":"Tyrosine – a structural glue for hierarchical protein assembly","authors":"Anton Maraldo ,&nbsp;Jelena Rnjak-Kovacina ,&nbsp;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":"49 7","pages":"Pages 633-648"},"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}
引用次数: 0
Optical tweezers microrheology maps micro-mechanics of complex systems 光学镊子微流变学绘制复杂系统的微观力学图。
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2024-07-01 DOI: 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":"49 7","pages":"Pages 649-650"},"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}
引用次数: 0
Subscription and Copyright Information 订阅和版权信息
IF 11.6 1区 生物学
Trends in Biochemical Sciences Pub Date : 2024-07-01 DOI: 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":"49 7","pages":"Page e1"},"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}
引用次数: 0
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