Quarterly Reviews of Biophysics最新文献

{"title":"Protein Data Bank (PDB): Fifty-three Years Young and Having a Transformative Impact on Science and Society.","authors":"Helen M Berman, Stephen K Burley","doi":"10.1017/S0033583525000034","DOIUrl":"https://doi.org/10.1017/S0033583525000034","url":null,"abstract":"","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":" ","pages":"1-50"},"PeriodicalIF":7.2,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143459312","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}

{"title":"Machinery, mechanism and information in post-transcription control of gene expression, from the perspective of unstable RNA.","authors":"Giulia Paris, Kai Katsuya-Gaviria, Ben Luisi","doi":"10.1017/S0033583525000022","DOIUrl":"https://doi.org/10.1017/S0033583525000022","url":null,"abstract":"","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":" ","pages":"1-42"},"PeriodicalIF":7.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123489","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}

{"title":"Dynamics and kinetics in structural biology: the example of DNA photolyase.","authors":"Keith Moffat","doi":"10.1017/S0033583524000222","DOIUrl":"10.1017/S0033583524000222","url":null,"abstract":"<p><p>All biochemical reactions directly involve structural changes that may occur over a very wide range of timescales from femtoseconds to seconds. Understanding the mechanism of action thus requires determination of both the static structures of the macromolecule involved and short-lived intermediates between reactant and product. This requires either freeze-trapping of intermediates, for example by cryo-electron microscopy, or direct determination of structures in active systems at near-physiological temperature by time-resolved X-ray crystallography. Storage ring X-ray sources effectively cover the time range down to around 100 ps that reveal tertiary and quaternary structural changes in proteins. The briefer pulses emitted by hard X-ray free electron laser sources extend that range to femtoseconds, which covers critical chemical reactions such as electron transfer, isomerization, breaking of covalent bonds, and ultrafast structural changes in light-sensitive protein chromophores and their protein environment. These reactions are exemplified by the time-resolved X-ray studies by two groups of the FAD-based DNA repair enzyme, DNA photolyase, over the time range from 1 ps to 100 μs.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":" ","pages":"e8"},"PeriodicalIF":7.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047728","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}

{"title":"Allostery.","authors":"Mateu Montserrat-Canals, Gabriele Cordara, Ute Krengel","doi":"10.1017/S0033583524000209","DOIUrl":"https://doi.org/10.1017/S0033583524000209","url":null,"abstract":"<p><p><i>Allostery</i> describes the ability of biological macromolecules to transmit signals spatially through the molecule from an <i>allosteric</i> site – a site that is distinct from <i>orthosteric</i> binding sites of primary, endogenous ligands – to the functional or active site. This review starts with a historical overview and a description of the classical example of allostery – hemoglobin – and other well-known examples (aspartate transcarbamoylase, Lac repressor, kinases, G-protein-coupled receptors, adenosine triphosphate synthase, and chaperonin). We then discuss fringe examples of allostery, including intrinsically disordered proteins and inter-enzyme allostery, and the influence of dynamics, entropy, and conformational ensembles and landscapes on allosteric mechanisms, to capture the essence of the field. Thereafter, we give an overview over central methods for investigating molecular mechanisms, covering experimental techniques as well as simulations and artificial intelligence (AI)-based methods. We conclude with a review of allostery-based drug discovery, with its challenges and opportunities: with the recent advent of AI-based methods, allosteric compounds are set to revolutionize drug discovery and medical treatments.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"58 ","pages":"e5"},"PeriodicalIF":7.2,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029367","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}

{"title":"S-layers: from a serendipitous discovery to a toolkit for nanobiotechnology.","authors":"Uwe B Sleytr, Dietmar Pum","doi":"10.1017/S0033583524000106","DOIUrl":"https://doi.org/10.1017/S0033583524000106","url":null,"abstract":"<p><p>Prokaryotic microorganisms, comprising <i>Bacteria</i> and <i>Archaea</i>, exhibit a fascinating diversity of cell envelope structures reflecting their adaptations that contribute to their resilience and survival in diverse environments. Among these adaptations, surface layers (S-layers) composed of monomolecular protein or glycoprotein lattices are one of the most observed envelope components. They are the most abundant cellular proteins and represent the simplest biological membranes that have developed during evolution. S-layers provide organisms with a great variety of selective advantages, including acting as an antifouling layer, protective coating, molecular sieve, ion trap, structure involved in cell and molecular adhesion, surface recognition and virulence factor for pathogens. In <i>Archaea</i> that possess S-layers as the exclusive cell wall component, the (glyco)protein lattices function as a cell shape-determining/maintaining scaffold. The wealth of information available on the structure, chemistry, genetics and <i>in vivo</i> and <i>in vitro</i> morphogenesis has revealed a broad application potential for S-layers as patterning elements in a molecular construction kit for bio- and nanotechnology, synthetic biology, biomimetics, biomedicine and diagnostics. In this review, we try to describe the scientifically exciting early days of S-layer research with a special focus on the 'Vienna-S-Layer-Group'. Our presentation is intended to illustrate how our curiosity and joy of discovery motivated us to explore this new structure and to make the scientific community aware of its relevance in the realm of prokaryotes, and moreover, how we developed concepts for exploiting this unique self-assembly structure. We hope that our presentation, with its many personal notes, is also of interest from the perspective of the history of S-layer research.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"58 ","pages":"e4"},"PeriodicalIF":7.2,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056058","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}

{"title":"From resting potential to dynamics: advances in membrane voltage indicators and imaging techniques.","authors":"Reyhaneh Shakibi, Fatemeh Yazdipour, Hamed Abadijoo, Navid Manoochehri, Farshid Rostami Pouria, Taraneh Bajooli, Hossein Simaee, Parviz Abdolmaleki, Ali Khatibi, Mohammad Abdolahad, Ali Akbar Moosavi-Movahhedi, Mohammad Ali Khayamian","doi":"10.1017/S0033583524000210","DOIUrl":"10.1017/S0033583524000210","url":null,"abstract":"<p><p>The membrane potential is a critical aspect of cellular physiology, essential for maintaining homeostasis, facilitating signal transduction, and driving various cellular processes. While the resting membrane potential (RMP) represents a key physiological parameter, membrane potential fluctuations, such as depolarization and hyperpolarization, are equally vital in understanding dynamic cellular behavior. Traditional techniques, such as microelectrodes and patch-clamp methods, offer valuable insights but are invasive and less suited for high-throughput applications. Recent advances in voltage indicators, including fast and slow dyes, and novel imaging modalities such as second harmonic generation (SHG) and photoacoustic imaging, enable noninvasive, high-resolution measurement of both RMP and membrane potential dynamics. This review explores the mechanisms, development, and applications of these tools, emphasizing their transformative potential in neuroscience and cellular electrophysiology research.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":" ","pages":"e7"},"PeriodicalIF":7.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009961","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}

{"title":"Molecular mechanisms of the GABA type A receptor function.","authors":"Michał A Michałowski, Karol Kłopotowski, Grzegorz Wiera, Marta M Czyżewska, Jerzy W Mozrzymas","doi":"10.1017/S0033583524000179","DOIUrl":"https://doi.org/10.1017/S0033583524000179","url":null,"abstract":"<p><p>The GABA type A receptor (GABA_AR) belongs to the family of pentameric ligand-gated ion channels and plays a key role in inhibition in adult mammalian brains. Dysfunction of this macromolecule may lead to epilepsy, anxiety disorders, autism, depression, and schizophrenia. GABA_AR is also a target for multiple physiologically and clinically relevant modulators, such as benzodiazepines (BDZs), general anesthetics, and neurosteroids. The first GABA_AR structure appeared in 2014, but the past years have brought a particularly abundant surge in structural data for these receptors with various ligands and modulators. Although the open conformation remains elusive, this novel information has pushed the structure-function studies to an unprecedented level. Electrophysiology, mutagenesis, photolabeling, and in silico simulations, guided by novel structural information, shed new light on the molecular mechanisms of receptor functioning. The main goal of this review is to present the current knowledge of GABA_AR functional and structural properties. The review begins with an outline of the functional and structural studies of GABA_AR, accompanied by some methodological considerations, especially biophysical methods, enabling the reader to follow how major breakthroughs in characterizing GABA_AR features have been achieved. The main section provides a comprehensive analysis of the functional significance of specific structural elements in GABA_ARs. We additionally summarize the current knowledge on the binding sites for major GABA_AR modulators, referring to the molecular underpinnings of their action. The final chapter of the review moves beyond examining GABA_AR as an isolated macromolecule and describes the interactions of the receptor with other proteins in a broader context of inhibitory plasticity. In the final section, we propose a general conclusion that agonist binding to the orthosteric binding sites appears to rely on local interactions, whereas conformational transitions of bound macromolecule (gating) and allosteric modulation seem to reflect more global phenomena involving vast portions of the macromolecule.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"58 ","pages":"e3"},"PeriodicalIF":7.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979875","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}

{"title":"Viroporins: discovery, methods of study, and mechanisms of host-membrane permeabilization.","authors":"Antonio Alcaraz, José L Nieva","doi":"10.1017/S0033583524000192","DOIUrl":"https://doi.org/10.1017/S0033583524000192","url":null,"abstract":"<p><p>The 'Viroporin' family comprises a number of mostly small-sized, integral membrane proteins encoded by animal and plant viruses. Despite their sequence and structural diversity, viroporins share a common functional trend: their capacity to assemble transmembrane channels during the replication cycle of the virus. Their selectivity spectrum ranges from low-pH-activated, unidirectional proton transporters, to size-limited permeating pores allowing passive diffusion of metabolites. Through mechanisms not fully understood, expression of viroporins facilitates virion assembly/release from infected cells, and subverts the cell physiology, contributing to cytopathogenicity. Compounds that interact with viroporins and interfere with their membrane-permeabilizing activity <i>in vitro</i>, are known to inhibit virus production. Moreover, viroporin-defective viruses comprise a source of live attenuated vaccines that prevent infection by notorious human and livestock pathogens. This review dives into the origin and evolution of the viroporin concept, summarizes some of the methodologies used to characterize the structure-function relationships of these important virulence factors, and attempts to classify them on biophysical grounds attending to their mechanisms of ion/solute transport across membranes.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"58 ","pages":"e1"},"PeriodicalIF":7.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979888","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}

{"title":"Structural biology inside multicellular specimens using electron cryotomography.","authors":"Ido Caspy, Zhexin Wang, Tanmay A M Bharat","doi":"10.1017/S0033583525000010","DOIUrl":"10.1017/S0033583525000010","url":null,"abstract":"<p><p>The electron cryomicroscopy (cryo-EM) resolution revolution has shifted structural biology into a new era, enabling the routine structure determination of macromolecular complexes at an unprecedented rate. Building on this, electron cryotomography (cryo-ET) offers the potential to visualise the native three-dimensional organisation of biological specimens, from cells to tissues and even entire organisms. Despite this huge potential, the study of tissue-like multicellular specimens via cryo-ET still presents numerous challenges, wherein many steps in the workflow are being developed or in urgent need of improvement. In this review, we outline the latest techniques currently utilised for <i>in situ</i> imaging of multicellular specimens, while clearly enumerating their associated limitations. We consider every step in typical workflows employed by various laboratories, including sample preparation, data collection and image analysis, to highlight recent progress and showcase prominent success stories. By considering the entire structural biology workflow for multicellular specimens, we identify which future exciting developments in hardware and software could enable comprehensive <i>in situ</i> structural biology investigations, bringing forth a new age of discovery in molecular structural and cell biology.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":" ","pages":"e6"},"PeriodicalIF":7.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7617309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972090","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}

{"title":"Life and death of Yfh1: how cool is cold denaturation.","authors":"Piero Andrea Temussi, Stephen R Martin, Annalisa Pastore","doi":"10.1017/S0033583524000180","DOIUrl":"https://doi.org/10.1017/S0033583524000180","url":null,"abstract":"<p><p>Yeast frataxin (Yfh1) is a small natural protein from yeast that has the unusual property of undergoing cold denaturation at temperatures above the freezing point of water when under conditions of low ionic strength. This peculiarity, together with remarkable resilience, allows the determination, for the whole protein as well as for individual residues, of the stability curve, that is the temperature dependence of the free energy difference between the unfolded and folded forms. The ease of measuring stability curves without the need to add denaturants or introduce <i>ad hoc</i> destabilizing mutations makes this protein an ideal 'tool' for investigating the influence of many environmental factors on protein stability. The present review aims at recapitulating all the open questions that Yfh1 has helped to address, including understanding the differences and commonalities of the cold, heat and pressure unfolded states. This protein thus offers a unique tool for studying aspects of protein stability so far been considered difficult to assess and provides important guidelines that could allow the identification of other similar systems.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"58 ","pages":"e2"},"PeriodicalIF":7.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972051","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}