Quarterly Reviews of Biophysics最新文献

{"title":"Determination of protein-protein interactions at the single-molecule level using optical tweezers.","authors":"Wendy N Sánchez,&nbsp;Luka Robeson,&nbsp;Valentina Carrasco,&nbsp;Nataniel L Figueroa,&nbsp;Francesca Burgos-Bravo,&nbsp;Christian A M Wilson,&nbsp;Nathalie Casanova-Morales","doi":"10.1017/S0033583522000075","DOIUrl":"https://doi.org/10.1017/S0033583522000075","url":null,"abstract":"<p><p>Biomolecular interactions are at the base of all physical processes within living organisms; the study of these interactions has led to the development of a plethora of different methods. Among these, single-molecule (<i>in singulo</i>) experiments have become relevant in recent years because these studies can give insight into mechanisms and interactions that are hidden for ensemble-based (<i>in multiplo</i>) methods. The focus of this review is on optical tweezer (OT) experiments, which can be used to apply and measure mechanical forces in molecular systems. OTs are based on optical trapping, where a laser is used to exert a force on a dielectric bead; and optically trap the bead at a controllable position in all three dimensions. Different experimental approaches have been developed to study protein–protein interactions using OTs, such as: (1) refolding and unfolding in <i>trans</i> interaction where one protein is tethered between the beads and the other protein is in the solution; (2) constant force in <i>cis</i> interaction where each protein is bound to a bead, and the tension is suddenly increased. The interaction may break after some time, giving information about the lifetime of the binding at that tension. And (3) force ramp in <i>cis</i> interaction where each protein is attached to a bead and a ramp force is applied until the interaction breaks. With these experiments, parameters such as kinetic constants (<i>k</i>_off, <i>k</i>_on), affinity values (<i>K</i>_D), energy to the transition state Δ<i>G</i>^≠, distance to the transition state Δ<i>x</i>^≠ can be obtained. These parameters characterize the energy landscape of the interaction. Some parameters such as distance to the transition state can only be obtained from force spectroscopy experiments such as those described here.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2022-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10732671","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":"The development of single molecule force spectroscopy: from polymer biophysics to molecular machines.","authors":"Carlos Bustamante,&nbsp;Shannon Yan","doi":"10.1017/S0033583522000087","DOIUrl":"https://doi.org/10.1017/S0033583522000087","url":null,"abstract":"<p><p>The advent of single-molecule force spectroscopy represents the introduction of forces, torques, and displacements as controlled variables in biochemistry. These methods afford the direct manipulation of individual molecules to interrogate the forces that hold together their structure, the forces and torques that these molecules generate in the course of their biochemical reactions, and the use of force, torque, and displacement as tools to investigate the mechanisms of these reactions. Because of their microscopic nature, the signals detected in these experiments are often dominated by fluctuations, which, in turn, play an important role in the mechanisms that underlie the operation of the molecular machines of the cell. Their direct observation and quantification in single-molecule experiments provide a unique window to investigate those mechanisms, as well as a convenient way to investigate fundamental new fluctuation theorems of statistical mechanics that bridge the equilibrium and non-equilibrium realms of this discipline. In this review we have concentrated on the developments that occurred in our laboratory on the characterization of biopolymers and of molecular machines of the central dogma. Accordingly, some important areas like the study of cytoskeletal motors have not been included. While we adopt at times an anecdotal perspective with the hope of conveying the personal circumstances in which these developments took place, we have made every effort, nonetheless, to include the most important developments that were taking place at the same time in other laboratories.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2022-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10713844","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":"Hiding in plain sight: three chemically distinct <i>α</i>-helix types.","authors":"Shuguang Zhang, Martin Egli","doi":"10.1017/S0033583522000063","DOIUrl":"10.1017/S0033583522000063","url":null,"abstract":"<p><p>Linus Pauling in 1950 published a three-dimensional model for a universal protein secondary structure motif which he initially called the alpha-spiral. Jack Dunitz, then a postdoc in Pauling's lab suggested to Pauling that the term helix is more accurate than spiral when describing the right-handed peptide and protein coiled structures. Pauling agreed, hence the rise of the alpha-helix, and, by extension, the ‘double helix’ structure of DNA. Although structural biologists and protein chemists are familiar with varying polar and apolar characters of amino acids in alpha-helices, to non-experts the three chemically distinct alpha-helix types classified here may hide in plain sight.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2022-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40058616","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":"When Alphafold2 predictions go wrong for protein–protein complexes, is there something to be learnt?","authors":"Juliette Martin","doi":"10.1017/S0033583522000051","DOIUrl":"https://doi.org/10.1017/S0033583522000051","url":null,"abstract":"Abstract In this short communication, I analyze cases of failed predictions for protein–protein complexes with Alphafold2, and show that they either point to erroneous annotation in the PDB or correct binding site regions.","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75771153","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":"Digging into the biophysical features of cell membranes with lipid-DNA conjugates.","authors":"Ahsan Ausaf Ali, Yousef Bagheri, Mingxu You","doi":"10.1017/S003358352200004X","DOIUrl":"10.1017/S003358352200004X","url":null,"abstract":"<p><p>Lipid-DNA conjugates have emerged as highly useful tools to modify the cell membranes. These conjugates generally consist of a lipid anchor for membrane modification and a functional DNA nanostructure for membrane analysis or regulation. There are several unique properties of these lipid-DNA conjugates, especially including their programmability, fast and efficient membrane insertion, and precise sequence-specific assembly. These unique properties have enabled a broad range of biophysical applications on live cell membranes. In this review, we will mainly focus on recent tremendous progress, especially during the past three years, in regulating the biophysical features of these lipid-DNA conjugates and their key applications in studying cell membrane biophysics. Some insights into the current challenges and future directions of this interdisciplinary field have also been provided.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":null,"pages":null},"PeriodicalIF":7.2,"publicationDate":"2022-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284422/pdf/nihms-1821360.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9824987","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":"The use of vector formalism in the analysis of hydrophobic and electric driving forces in biological assemblies.","authors":"Angel Mozo-Villarías, Juan A Cedano, Enrique Querol","doi":"10.1017/S0033583522000038","DOIUrl":"10.1017/S0033583522000038","url":null,"abstract":"","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87765617","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":"Studies of cell-penetrating peptides by biophysical methods.","authors":"Matjaž Zorko, Ülo Langel","doi":"10.1017/S0033583522000026","DOIUrl":"10.1017/S0033583522000026","url":null,"abstract":"","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84600508","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":"Structures of synthetic helical filaments and tubes based on peptide and peptido-mimetic polymers.","authors":"Jessalyn G Miller, Spencer A Hughes, Charles Modlin, Vincent P Conticello","doi":"10.1017/S0033583522000014","DOIUrl":"10.1017/S0033583522000014","url":null,"abstract":"","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2022-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91254790","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":"Differential repair enzyme-substrate selection within dynamic DNA energy landscapes.","authors":"J Völker,&nbsp;K J Breslauer","doi":"10.1017/S0033583521000093","DOIUrl":"https://doi.org/10.1017/S0033583521000093","url":null,"abstract":"<p><p>We demonstrate that reshaping of the dynamic, bulged-loop energy landscape of DNA triplet repeat ensembles by the presence of an abasic site alters repair outcomes by the APE1 enzyme. This phenomenon depends on the structural context of the lesion, despite the abasic site always having the same neighbors in sequence space. We employ this lesion-induced redistribution of DNA states and a kinetic trap to monitor different occupancies of the DNA bulge loop states. We show how such dynamic redistribution and associated differential occupancies of DNA states impact APE1 repair outcomes and APE1 induced interconversions. We correlate the differential biophysical properties of the dynamic, DNA ensemble states, with their ability to be recognized and processed as substrates by the APE1 DNA repair enzyme. Enzymatic digestions and biophysical characterizations reveal that APE1 cuts a fraction (10-12%) of the dynamic, rollameric substrates within the initial kinetic distribution. APE1 interactions also 'induce' rollamer redistribution from a kinetically trapped distribution to an equilibrium distribution, the latter not containing viable APE1 substrates. We distinguish between kinetically controlled ensemble (re)distributions of potential DNA substrates, versus thermodynamically controlled ensemble (re)distribution; features of importance to DNA regulation. We conclude that APE1 activity catalyzes/induces ensembles that represent the thermodynamically optimal loop distribution, yet which also are nonviable substrate states for abasic site cleavage by APE1. We propose that by inducing substrate redistributions in a dynamic energy landscape, the enzyme actually reduces the available substrate competent species for it to process, reflective of a regulatory mechanism for enzymatic self-repression. If this is a general phenomenon, such a consequence would have a profound impact on slowing down and/or misdirecting DNA repair within dynamic energy landscapes, as exemplified here within triplet repeat domains. In short, APE1-instigated redistribution of potential substrates induces a preferred pathway to an equilibrium ensemble of enzymatically incompetent states.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2021-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39945924","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":"The mechanics of mitotic chromosomes.","authors":"T Man,&nbsp;H Witt,&nbsp;E J G Peterman,&nbsp;G J L Wuite","doi":"10.1017/S0033583521000081","DOIUrl":"https://doi.org/10.1017/S0033583521000081","url":null,"abstract":"<p><p>Condensation and faithful separation of the genome are crucial for the cellular life cycle. During chromosome segregation, mechanical forces generated by the mitotic spindle pull apart the sister chromatids. The mechanical nature of this process has motivated a lot of research interest into the mechanical properties of mitotic chromosomes. Although their fundamental mechanical characteristics are known, it still remains unclear how these characteristics emerge from the structure of the mitotic chromosome. Recent advances in genomics, computational and super-resolution microscopy techniques have greatly promoted our understanding of the chromosomal structure and have motivated us to review the mechanical characteristics of chromosomes in light of the current structural insights. In this review, we will first introduce the current understanding of the chromosomal structure, before reviewing characteristic mechanical properties such as the Young's modulus and the bending modulus of mitotic chromosomes. Then we will address the approaches used to relate mechanical properties to the structure of chromosomes and we will also discuss how mechanical characterization can aid in elucidating their structure. Finally, future challenges, recent developments and emergent questions in this research field will be discussed.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2021-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39423350","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}