Current opinion in structural biology最新文献

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Photo-crosslinkers boost structural information from crosslinking mass spectrometry 光交联剂提高结构信息从交联质谱
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-07-04 DOI: 10.1016/j.sbi.2025.103102
Anthony Ciancone, Francis J. O'Reilly
{"title":"Photo-crosslinkers boost structural information from crosslinking mass spectrometry","authors":"Anthony Ciancone,&nbsp;Francis J. O'Reilly","doi":"10.1016/j.sbi.2025.103102","DOIUrl":"10.1016/j.sbi.2025.103102","url":null,"abstract":"<div><div>Crosslinking mass spectrometry has emerged as a powerful tool in structural biology. This technology utilizes chemical crosslinkers to capture spatial proximities between protein residues to probe the organization, stoichiometry, and flexibility of protein assemblies under near-native conditions. Photo-crosslinking reagents have become increasingly used in crosslinking MS, with chemical properties that offer significant advantages when studying dynamic protein structures. This review explores the fundamentals, applications, and future potential of photo-crosslinkers in crosslinking mass spectrometry.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"93 ","pages":"Article 103102"},"PeriodicalIF":6.1,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563737","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
Review: Membrane protein nanodiscs for antibody discovery 综述:用于抗体发现的膜蛋白纳米片
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-07-03 DOI: 10.1016/j.sbi.2025.103104
Xiaojie Yao , Christy A. Thomson
{"title":"Review: Membrane protein nanodiscs for antibody discovery","authors":"Xiaojie Yao ,&nbsp;Christy A. Thomson","doi":"10.1016/j.sbi.2025.103104","DOIUrl":"10.1016/j.sbi.2025.103104","url":null,"abstract":"<div><div>Membrane proteins play pivotal roles in cellular signaling, transport, and immune responses. Dysregulation of these proteins frequently underlies diverse disease states, making them appealing targets for drug development, including therapeutic antibodies. Traditionally, the extraction and stabilization of membrane proteins involve detergents, which may compromise the protein's native conformation, thus impeding antibody discovery. The shift toward detergent-free formulations using membrane protein nanodiscs formed by membrane scaffold proteins (MSPs), copolymers, saposins, or peptides has opened new avenues in membrane protein research and antibody discovery. They allow for the stabilization of membrane proteins in a more native-like environment, preserving structural integrity and function. This review discusses various membrane protein nanodiscs, and their applications in antibody discovery, alongside current advancements and challenges.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"94 ","pages":"Article 103104"},"PeriodicalIF":6.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144535514","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
All-atom simulations of biomolecular condensates 生物分子凝聚物的全原子模拟
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-07-03 DOI: 10.1016/j.sbi.2025.103101
Miloš T. Ivanović , Robert B. Best
{"title":"All-atom simulations of biomolecular condensates","authors":"Miloš T. Ivanović ,&nbsp;Robert B. Best","doi":"10.1016/j.sbi.2025.103101","DOIUrl":"10.1016/j.sbi.2025.103101","url":null,"abstract":"<div><div>Biomolecular condensates shape a wide spectrum of physiological and pathological processes, yet the molecular mechanisms underlying their formation and activity are still to be fully understood. Molecular simulations can provide valuable insights into the structure and dynamics of such condensates, and coarse-grained simulations have been widely used to characterize phenomena related to their phase equilibrium. All-atom simulations provide a complementary picture–while too expensive to readily study equilibrium between dense and dilute phases, they offer molecular detail on the dense phase that is missing from coarse-grained models, as well as accurate dynamical information. We provide an overview of this nascent application of atomistic simulations to condensates and the insights they have yielded on their structure and dynamics.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"93 ","pages":"Article 103101"},"PeriodicalIF":6.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144536129","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
Editorial overview: Sequences and topology (2025) 编辑概述:序列和拓扑(2025)
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-07-01 DOI: 10.1016/j.sbi.2025.103108
Arne Elofsson, Rachel Kolodny
{"title":"Editorial overview: Sequences and topology (2025)","authors":"Arne Elofsson,&nbsp;Rachel Kolodny","doi":"10.1016/j.sbi.2025.103108","DOIUrl":"10.1016/j.sbi.2025.103108","url":null,"abstract":"","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"93 ","pages":"Article 103108"},"PeriodicalIF":6.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518540","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
To tilt or not to tilt? Strategies for in situ cryo-EM data collection 倾斜还是不倾斜?原位低温电镜数据收集策略
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-06-28 DOI: 10.1016/j.sbi.2025.103100
Joshua L. Dickerson , Bronwyn A. Lucas
{"title":"To tilt or not to tilt? Strategies for in situ cryo-EM data collection","authors":"Joshua L. Dickerson ,&nbsp;Bronwyn A. Lucas","doi":"10.1016/j.sbi.2025.103100","DOIUrl":"10.1016/j.sbi.2025.103100","url":null,"abstract":"<div><div>Recent breakthroughs in single-particle cryogenic electron microscopy (cryo-EM) and protein structure prediction have transformed our ability to resolve molecular structures. Since we have now experimentally determined, or can confidently predict, the structures of a significant portion of the proteome, and since workflows for imaging in cells are established, the stage is set for applying cryo-EM to understand the molecular basis of complex cellular functions. This review explores a spectrum of data collection strategies—from 2D approaches to tomography—used for <em>in situ</em> cryo-EM. We discuss their relative merits in addressing key biological questions and the need to tailor them towards experimental goals. Improvements in theoretical and practical understanding of the challenges for <em>in situ</em> cryo-EM are necessary for optimizing data collection strategies and pushing the boundaries of structural cell biology.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"93 ","pages":"Article 103100"},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501641","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 influence of lipids and biological membranes on the conformational equilibria of GPCRs: Insights from NMR spectroscopy 脂质和生物膜对gpcr构象平衡的影响:来自核磁共振光谱的见解
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-06-27 DOI: 10.1016/j.sbi.2025.103103
Greeshma Jain, Matthew T. Eddy
{"title":"The influence of lipids and biological membranes on the conformational equilibria of GPCRs: Insights from NMR spectroscopy","authors":"Greeshma Jain,&nbsp;Matthew T. Eddy","doi":"10.1016/j.sbi.2025.103103","DOIUrl":"10.1016/j.sbi.2025.103103","url":null,"abstract":"<div><div>G protein-coupled receptors (GPCRs) function within cellular membranes, complex and dynamic environments. Rather than serving as a passive background, lipid membranes actively influence GPCR drug responses and signaling. Studies utilizing nuclear magnetic resonance (NMR) spectroscopy have revealed key insights into receptor–lipid interactions, enabled by the compatibility of NMR experiments with many different membrane systems and physiological temperature, conditions more closely reflecting the native cellular environment. NMR data have revealed new mechanistic insights that explain how specific lipids regulate GPCR activation, how bulk membrane properties influence receptor dynamics, and how different membrane mimetics affect GPCR behavior. These findings establish a framework for bridging <em>in vitro</em> structural studies with <em>in vivo</em> biological and pharmacological data.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"94 ","pages":"Article 103103"},"PeriodicalIF":6.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490412","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
Fuzziness in enzymatic catalysis 酶催化的模糊性
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-06-27 DOI: 10.1016/j.sbi.2025.103106
Sachin S. Katti , Tvesha Parikh , Rachel J. Godek , Rebecca Page , Wolfgang Peti
{"title":"Fuzziness in enzymatic catalysis","authors":"Sachin S. Katti ,&nbsp;Tvesha Parikh ,&nbsp;Rachel J. Godek ,&nbsp;Rebecca Page ,&nbsp;Wolfgang Peti","doi":"10.1016/j.sbi.2025.103106","DOIUrl":"10.1016/j.sbi.2025.103106","url":null,"abstract":"<div><div>Intrinsically disordered proteins/regions (IDPs/IDRs) frequently engage in dynamic charge:charge interactions, commonly referred to as ‘fuzzy’ interactions. These fuzzy interactions play critical roles in enzymatic regulation and substrate recruitment, especially for protein kinases and protein phosphatases. Here, we review recent advances that demonstrate how inter- and intramolecular fuzzy interactions among kinases and phosphatases and their cognate regulators and substrates allow for enzyme assembly, activation and substrate recruitment. We also highlight a unique mechanism of protein inhibition, where a protein phosphatase is inhibited by dynamic fuzzy interactions with its active site metals.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"93 ","pages":"Article 103106"},"PeriodicalIF":6.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490450","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
Applications of high-throughput reporter assays to gene regulation studies 高通量报告基因检测在基因调控研究中的应用
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-06-27 DOI: 10.1016/j.sbi.2025.103105
Benedetta D'Elia , Juan Fuxman Bass
{"title":"Applications of high-throughput reporter assays to gene regulation studies","authors":"Benedetta D'Elia ,&nbsp;Juan Fuxman Bass","doi":"10.1016/j.sbi.2025.103105","DOIUrl":"10.1016/j.sbi.2025.103105","url":null,"abstract":"<div><div>Determining the rules of transcriptional regulation, associated with a complex transcription factor grammar, is fundamental to understand the control of most biological processes, disease mechanisms, and evolution. High-throughput reporter assays, such as MPRAs and STARR-seq, have enabled systematic functional annotations of genomes and have provided large substrates for training machine learning models to determine these rules, predict the activity of native and synthetic elements, and design elements for different applications. This review provides an overview of high-throughput reporter assays and their applications for the study of enhancers, promoters, silencers and insulators. We discuss how these assays help identify causal disease-associated non-coding variants and design synthetic elements with desired features for functional studies or therapeutic purposes.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"94 ","pages":"Article 103105"},"PeriodicalIF":6.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490413","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
Editorial overview by Philip Biggin (University of Oxford) and Roderick Hubbard (University of York) 2025 issue of Current Opinion in Structural Biology - New Concepts in Drug Discovery (2025) Philip Biggin(牛津大学)和Roderick Hubbard(约克大学)编辑概述2025年结构生物学当前观点-药物发现的新概念(2025)
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-06-26 DOI: 10.1016/j.sbi.2025.103069
Philip C. Biggin, Roderick E. Hubbard
{"title":"Editorial overview by Philip Biggin (University of Oxford) and Roderick Hubbard (University of York) 2025 issue of Current Opinion in Structural Biology - New Concepts in Drug Discovery (2025)","authors":"Philip C. Biggin,&nbsp;Roderick E. Hubbard","doi":"10.1016/j.sbi.2025.103069","DOIUrl":"10.1016/j.sbi.2025.103069","url":null,"abstract":"","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"93 ","pages":"Article 103069"},"PeriodicalIF":6.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490451","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
Bioreactor in-cell NMR: A powerful tool for observing intracellular biological events 细胞内生物反应器核磁共振:一种观察细胞内生物事件的强大工具
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2025-06-26 DOI: 10.1016/j.sbi.2025.103086
Noritaka Nishida , Qingci Zhao , Ichio Shimada
{"title":"Bioreactor in-cell NMR: A powerful tool for observing intracellular biological events","authors":"Noritaka Nishida ,&nbsp;Qingci Zhao ,&nbsp;Ichio Shimada","doi":"10.1016/j.sbi.2025.103086","DOIUrl":"10.1016/j.sbi.2025.103086","url":null,"abstract":"<div><div>Unlike conventional biochemical and cell biological methods, in-cell NMR enables direct observation of intracellular protein structures and dynamics at atomic resolution in their native cellular environment. However, a key challenge is maintaining cell viability during prolonged measurements, as nutrient depletion leads to rapid cell death and protein degradation. To address this, bioreactor systems have been developed to perfuse culture media, enabling long-term NMR experiments. Bioreactor-based in-cell NMR has enabled real-time observation of function-related structural information of proteins, which are involved in various intracellular events, such as signal transduction, oxidative stress responses, and glycolytic regulation. Additionally, in-cell NMR has been applied to drug discovery, allowing assessment of drug binding kinetics, intracellular permeability, and target engagement within living cells.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"93 ","pages":"Article 103086"},"PeriodicalIF":6.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480166","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
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