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Fuzzy protein-DNA interactions and beyond: A common theme in transcription? 模糊的蛋白质-DNA相互作用及其他：转录的共同主题？
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-10-17 DOI: 10.1016/j.sbi.2024.102941
Elisabeth Komives , Ricardo Sanchez-Rodriguez , Hamed Taghavi , Monika Fuxreiter
{"title":"Fuzzy protein-DNA interactions and beyond: A common theme in transcription?","authors":"Elisabeth Komives ,&nbsp;Ricardo Sanchez-Rodriguez ,&nbsp;Hamed Taghavi ,&nbsp;Monika Fuxreiter","doi":"10.1016/j.sbi.2024.102941","DOIUrl":"10.1016/j.sbi.2024.102941","url":null,"abstract":"<div><div>Gene expression regulation requires both diversity and specificity. How can these two contradictory conditions be reconciled? Dynamic DNA recognition mechanisms lead to heterogeneous bound conformations, which can be shifted by the cellular cues. Here we summarise recent experimental evidence on how fuzzy interactions contribute to chromatin remodelling, regulation of DNA replication and repair and transcription factor binding. We describe how the binding mode continuum between DNA and regulatory factors lead to variable, multisite contact patterns; polyelectrolyte competitions; on-the-fly shape readouts; autoinhibition controlled by posttranslational modifications or dynamic oligomerisation mechanisms. Increasing experimental evidence supports the rugged energy landscape of the bound protein-DNA assembly, modulation of which leads to distinct functional outcomes. Recent results suggest the evolutionary conservation of these combinatorial mechanisms with moderate sequence constraints in the malleable transcriptional machinery.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102941"},"PeriodicalIF":6.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445949","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}
引用次数: 0
Extracellular DNA-protein interactions 细胞外 DNA 蛋白相互作用
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-10-16 DOI: 10.1016/j.sbi.2024.102943
Steven D. Goodman
{"title":"Extracellular DNA-protein interactions","authors":"Steven D. Goodman","doi":"10.1016/j.sbi.2024.102943","DOIUrl":"10.1016/j.sbi.2024.102943","url":null,"abstract":"<div><div>Intracellular DNA primarily serves as the cellular genetic material both in eukaryotes and prokaryotes. This function is often regulated by alterations in the DNA structure to accommodate transcription, recombination, and DNA replication. Extracellularly, both eukaryotic and prokaryotic cells take advantage of DNA plenty in addition to a permissive environment and create novel structures to fulfill multiple new roles. As often occurs intracellularly, extracellular DNA requires proteins to facilitate and stabilize these important structures. Here I review, both host and eubacterial nucleoprotein structures, their composition, their functions, and how these distinct structures can interact. Even at this early stage of study, it is clear that extracellular chromatin plays important biological roles in the survival of both prokaryotic and eukaryotic organisms.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102943"},"PeriodicalIF":6.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441592","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}
引用次数: 0
Nexus between RNA conformational dynamics and functional versatility RNA 构象动力学与功能多样性之间的联系
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-10-15 DOI: 10.1016/j.sbi.2024.102942
Yun-Tzai Lee
{"title":"Nexus between RNA conformational dynamics and functional versatility","authors":"Yun-Tzai Lee","doi":"10.1016/j.sbi.2024.102942","DOIUrl":"10.1016/j.sbi.2024.102942","url":null,"abstract":"<div><div>RNA conformational dynamics is pivotal for functional regulations in biology. RNA can function as versatile as protein but adopts multiple distinct structures. In this review, we provide a focused review of the recent advances in studies of RNA conformational dynamics and address some of the misconceptions about RNA structure and its conformational dynamics. We discuss why the traditional methods for structure determination come up short in describing RNA conformational space. The examples discussed provide illustrations of the structure-based mechanisms of RNAs with diverse roles, including viral, long noncoding, and catalytic RNAs, one of which focuses on the debated area of conformational heterogeneity of an RNA structural element in the HIV-1 genome.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102942"},"PeriodicalIF":6.1,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142438440","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}
引用次数: 0
RNA ensembles from in vitro to in vivo: Toward predictive models of RNA cellular function 从体外到体内的 RNA 组合：建立 RNA 细胞功能预测模型
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-10-13 DOI: 10.1016/j.sbi.2024.102915
Catherine Y. Li , Shawn Sandhu , Megan L. Ken
{"title":"RNA ensembles from in vitro to in vivo: Toward predictive models of RNA cellular function","authors":"Catherine Y. Li ,&nbsp;Shawn Sandhu ,&nbsp;Megan L. Ken","doi":"10.1016/j.sbi.2024.102915","DOIUrl":"10.1016/j.sbi.2024.102915","url":null,"abstract":"<div><div>Deepening our understanding of RNA biology and accelerating development of RNA-based therapeutics go hand-in-hand—both requiring a transition from qualitative descriptions of RNA structure to quantitative models capable of predicting RNA behaviors, and from a static to an ensemble view. Ensembles are determined from their free energy landscapes, which define the relative populations of conformational states and the energetic barriers separating them. Experimental determination of RNA ensembles over the past decade has led to powerful predictive models of RNA behavior <em>in vitro</em>. It has also been shown during this time that the cellular environment redistributes RNA ensembles, changing the abundances of functionally relevant conformers relative to <em>in vitro</em> contexts with subsequent functional RNA consequences. However, recent studies have demonstrated that testing models built from <em>in vitro</em> ensembles with highly quantitative measurements of RNA cellular function, aided by emerging computational methodologies, enables predictive modelling of cellular activity and biological discovery.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102915"},"PeriodicalIF":6.1,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433909","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}
引用次数: 0
Latent allosteric control of protein interactions by ATP-competitive kinase inhibitors ATP 竞争性激酶抑制剂对蛋白质相互作用的潜伏异构控制
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-10-11 DOI: 10.1016/j.sbi.2024.102935
David Vaisar, Natalie G. Ahn
{"title":"Latent allosteric control of protein interactions by ATP-competitive kinase inhibitors","authors":"David Vaisar,&nbsp;Natalie G. Ahn","doi":"10.1016/j.sbi.2024.102935","DOIUrl":"10.1016/j.sbi.2024.102935","url":null,"abstract":"<div><div>Protein kinase inhibitors designed to compete with ATP as a primary mode of action turn out to have considerable effects that go beyond their interference of nucleotide binding. New research shows how kinase activation and sometimes noncatalytic functions of protein kinases can be controlled by allosteric properties of kinase inhibitors, communicating perturbations from the active site to distal regulatory regions.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102935"},"PeriodicalIF":6.1,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142422870","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}
引用次数: 0
Engineering the native ensemble to tune protein function: Diverse mutational strategies and interlinked molecular mechanisms 设计原生组合以调整蛋白质功能：多种突变策略和相互关联的分子机制
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-10-10 DOI: 10.1016/j.sbi.2024.102940
Adithi Kannan, Athi N. Naganathan
{"title":"Engineering the native ensemble to tune protein function: Diverse mutational strategies and interlinked molecular mechanisms","authors":"Adithi Kannan,&nbsp;Athi N. Naganathan","doi":"10.1016/j.sbi.2024.102940","DOIUrl":"10.1016/j.sbi.2024.102940","url":null,"abstract":"<div><div>Natural proteins are fragile entities, intrinsically sensitive to perturbations both at the level of sequence and their immediate environment. Here, we highlight the diverse strategies available for engineering function through mutations influencing backbone conformational entropy, charge–charge interactions, and in the loops and hinge regions, many of which are located far from the active site. It thus appears that there are potentially numerous ways to microscopically vary the identity of residues and the constituent interactions to tune function. Functional modulation could occur via changes in native-state stability, altered thermodynamic coupling extents within the folded structure, redistributed dynamics, or through modulation of the population of conformational substates. As these mechanisms are intrinsically linked and given the pervasive long-range effects of mutations, it is crucial to consider the interaction network as a whole and fully map the native conformational landscape to place mutational effects in the context of allostery and protein evolution.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102940"},"PeriodicalIF":6.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406223","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}
引用次数: 0
Exascale simulations and beyond 超大规模模拟及其他
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-10-05 DOI: 10.1016/j.sbi.2024.102939
Paolo Carloni, Karissa Sanbonmatsu
{"title":"Exascale simulations and beyond","authors":"Paolo Carloni,&nbsp;Karissa Sanbonmatsu","doi":"10.1016/j.sbi.2024.102939","DOIUrl":"10.1016/j.sbi.2024.102939","url":null,"abstract":"","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102939"},"PeriodicalIF":6.1,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377766","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}
引用次数: 0
Recent advances in correlative cryo-light and electron microscopy 相关冷冻光镜和电子显微镜的最新进展。
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-10-03 DOI: 10.1016/j.sbi.2024.102934
Joshua A. Pierson , Jie E. Yang , Elizabeth R. Wright
{"title":"Recent advances in correlative cryo-light and electron microscopy","authors":"Joshua A. Pierson ,&nbsp;Jie E. Yang ,&nbsp;Elizabeth R. Wright","doi":"10.1016/j.sbi.2024.102934","DOIUrl":"10.1016/j.sbi.2024.102934","url":null,"abstract":"<div><div>Correlative light and electron microscopy (CLEM) pipelines serve to integrate the imaging modalities of fluorescence light microscopy (FLM) and cryogenic electron microscopy (cryo-EM) to produce contextually relevant high-resolution structural snapshots of biological systems. Innovations in sample preparation, instrumentation, imaging, and data processing have advanced the field of cryo-EM. This review focuses on prior work and recent developments in the field of cryo- EM that support further integration of technologies for correlative microscopy workflows.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102934"},"PeriodicalIF":6.1,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375278","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}
引用次数: 0
The role of RNA structure in 3’ end processing in eukaryotes 真核生物中 RNA 结构在 3' 端处理过程中的作用。
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-09-29 DOI: 10.1016/j.sbi.2024.102933
Jin Xu, Susan Duncan, Yiliang Ding
{"title":"The role of RNA structure in 3’ end processing in eukaryotes","authors":"Jin Xu,&nbsp;Susan Duncan,&nbsp;Yiliang Ding","doi":"10.1016/j.sbi.2024.102933","DOIUrl":"10.1016/j.sbi.2024.102933","url":null,"abstract":"<div><div>Maturation of pre-mRNA into fully functional mRNA involves a series of highly coordinated steps that are essential for eukaryotic gene expression. RNA structure has been found to play regulatory roles in many of these steps, including cleavage, polyadenylation, and termination. Recent advances in structure probing techniques have been instrumental in revealing how nascent transcript conformation contributes to these dynamic, co-transcriptional processes. In this review, we present examples where RNA structure affects accessibility and/or function of key processing enzymes, thereby influencing the efficiency and precision of 3′ end processing machinery. We also discuss emerging technologies that could further enhance our understanding of RNA structure mediated regulation of 3’ end processing.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102933"},"PeriodicalIF":6.1,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343309","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}
引用次数: 0
Using residue interaction networks to understand protein function and evolution and to engineer new proteins 利用残基相互作用网络了解蛋白质功能和进化，并设计新蛋白质
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-09-26 DOI: 10.1016/j.sbi.2024.102922
Dariia Yehorova , Bruno Di Geronimo , Michael Robinson , Peter M. Kasson , Shina C.L. Kamerlin
{"title":"Using residue interaction networks to understand protein function and evolution and to engineer new proteins","authors":"Dariia Yehorova ,&nbsp;Bruno Di Geronimo ,&nbsp;Michael Robinson ,&nbsp;Peter M. Kasson ,&nbsp;Shina C.L. Kamerlin","doi":"10.1016/j.sbi.2024.102922","DOIUrl":"10.1016/j.sbi.2024.102922","url":null,"abstract":"<div><div>Residue interaction networks (RINs) provide graph-based representations of interaction networks within proteins, providing important insight into the factors driving protein structure, function, and stability relationships. There exists a wide range of tools with which to perform RIN analysis, taking into account different types of interactions, input (crystal structures, simulation trajectories, single proteins, or comparative analysis across proteins), as well as formats, including standalone software, web server, and a web application programming interface (API). In particular, the ability to perform comparative RIN analysis across protein families using “metaRINs” provides a valuable tool with which to dissect protein evolution. This, in turn, highlights hotspots to avoid (or target) for <em>in vitro</em> evolutionary studies, providing a powerful framework that can be exploited to engineer new proteins.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102922"},"PeriodicalIF":6.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324158","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}
引用次数: 0
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