Quarterly Reviews of Biophysics最新文献

{"title":"Energy mapping of the genetic code and genomic domains: implications for code evolution and molecular Darwinism - CORRIGENDUM.","authors":"Horst H Klump, Jens Völker, Kenneth J Breslauer","doi":"10.1017/S0033583520000116","DOIUrl":"https://doi.org/10.1017/S0033583520000116","url":null,"abstract":"","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"53 ","pages":"e14"},"PeriodicalIF":6.1,"publicationDate":"2020-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583520000116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38696135","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":"Biophysical studies of protein misfolding and aggregation in <i>in vivo</i> models of Alzheimer's and Parkinson's diseases - ERRATUM.","authors":"Tessa Sinnige,&nbsp;Karen Stroobants,&nbsp;Christopher M Dobson,&nbsp;Michele Vendruscolo","doi":"10.1017/S0033583520000104","DOIUrl":"https://doi.org/10.1017/S0033583520000104","url":null,"abstract":"Neurodegenerative disorders, including Alzheimer's (AD) and Parkinson's diseases (PD), are characterised by the formation of aberrant assemblies of misfolded proteins. The discovery of disease-modifying drugs for these disorders is challenging, in part because we still have a limited understanding of their molecular origins. In this review, we discuss how biophysical approaches can help explain the formation of the aberrant conformational states of proteins whose neurotoxic effects underlie these diseases. We discuss in particular models based on the transgenic expression of amyloid-β (Aβ) and tau in AD, and α-synuclein in PD. Because biophysical methods have enabled an accurate quantification and a detailed understanding of the molecular mechanisms underlying protein misfolding and aggregation in vitro, we expect that the further development of these methods to probe directly the corresponding mechanisms in vivo will open effective routes for diagnostic and therapeutic interventions.","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"53 ","pages":"e13"},"PeriodicalIF":6.1,"publicationDate":"2020-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583520000104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38613457","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":"Single-molecule studies of amyloid proteins: from biophysical properties to diagnostic perspectives.","authors":"Jinming Wu,&nbsp;Chan Cao,&nbsp;Rolf Antonie Loch,&nbsp;Ann Tiiman,&nbsp;Jinghui Luo","doi":"10.1017/S0033583520000086","DOIUrl":"https://doi.org/10.1017/S0033583520000086","url":null,"abstract":"<p><p>In neurodegenerative diseases, a wide range of amyloid proteins or peptides such as amyloid-beta and α-synuclein fail to keep native functional conformations, followed by misfolding and self-assembling into a diverse array of aggregates. The aggregates further exert toxicity leading to the dysfunction, degeneration and loss of cells in the affected organs. Due to the disordered structure of the amyloid proteins, endogenous molecules, such as lipids, are prone to interact with amyloid proteins at a low concentration and influence amyloid cytotoxicity. The heterogeneity of amyloid proteinscomplicates the understanding of the amyloid cytotoxicity when relying only on conventional bulk and ensemble techniques. As complementary tools, single-molecule techniques (SMTs) provide novel insights into the different subpopulations of a heterogeneous amyloid mixture as well as the cytotoxicity, in particular as involved in lipid membranes. This review focuses on the recent advances of a series of SMTs, including single-molecule fluorescence imaging, single-molecule force spectroscopy and single-nanopore electrical recording, for the understanding of the amyloid molecular mechanism. The working principles, benefits and limitations of each technique are discussed and compared in amyloid protein related studies.. We also discuss why SMTs show great potential and are worthy of further investigation with feasibility studies as diagnostic tools of neurodegenerative diseases and which limitations are to be addressed.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"53 ","pages":"e12"},"PeriodicalIF":6.1,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583520000086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38566627","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":"Energy mapping of the genetic code and genomic domains: implications for code evolution and molecular Darwinism.","authors":"Horst H Klump,&nbsp;Jens Völker,&nbsp;Kenneth J Breslauer","doi":"10.1017/S0033583520000098","DOIUrl":"https://doi.org/10.1017/S0033583520000098","url":null,"abstract":"<p><p>When the iconic DNA genetic code is expressed in terms of energy differentials, one observes that information embedded in chemical sequences, including some biological outcomes, correlate with distinctive free energy profiles. Specifically, we find correlations between codon usage and codon free energy, suggestive of a thermodynamic selection for codon usage. We also find correlations between what are considered ancient amino acids and high codon free energy values. Such correlations may be reflective of the sequence-based genetic code fundamentally mapping as an energy code. In such a perspective, one can envision the genetic code as composed of interlocking thermodynamic cycles that allow codons to 'evolve' from each other through a series of sequential transitions and transversions, which are influenced by an energy landscape modulated by both thermodynamic and kinetic factors. As such, early evolution of the genetic code may have been driven, in part, by differential energetics, as opposed exclusively by the functionality of any gene product. In such a scenario, evolutionary pressures can, in part, derive from the optimization of biophysical properties (e.g. relative stabilities and relative rates), in addition to the classic perspective of being driven by a phenotypical adaptive advantage (natural selection). Such differential energy mapping of the genetic code, as well as larger genomic domains, may reflect an energetically resolved and evolved genomic landscape, consistent with a type of differential, energy-driven 'molecular Darwinism'. It should not be surprising that evolution of the code was influenced by differential energetics, as thermodynamics is the most general and universal branch of science that operates over all time and length scales.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"53 ","pages":"e11"},"PeriodicalIF":6.1,"publicationDate":"2020-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583520000098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38658152","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":"Exploring the dynamics of flagellar dynein within the axoneme with Fluctuating Finite Element Analysis.","authors":"Robin A Richardson,&nbsp;Benjamin S Hanson,&nbsp;Daniel J Read,&nbsp;Oliver G Harlen,&nbsp;Sarah A Harris","doi":"10.1017/S0033583520000062","DOIUrl":"https://doi.org/10.1017/S0033583520000062","url":null,"abstract":"<p><p>Flagellar dyneins are the molecular motors responsible for producing the propagating bending motions of cilia and flagella. They are located within a densely packed and highly organised super-macromolecular cytoskeletal structure known as the axoneme. Using the mesoscale simulation technique Fluctuating Finite Element Analysis (FFEA), which represents proteins as viscoelastic continuum objects subject to explicit thermal noise, we have quantified the constraints on the range of molecular conformations that can be explored by dynein-c within the crowded architecture of the axoneme. We subsequently assess the influence of crowding on the 3D exploration of microtubule-binding sites, and specifically on the axial step length. Our calculations combine experimental information on the shape, flexibility and environment of dynein-c from three distinct sources; negative stain electron microscopy, cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET). Our FFEA simulations show that the super-macromolecular organisation of multiple protein complexes into higher-order structures can have a significant influence on the effective flexibility of the individual molecular components, and may, therefore, play an important role in the physical mechanisms underlying their biological function.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"53 ","pages":"e9"},"PeriodicalIF":6.1,"publicationDate":"2020-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583520000062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38244889","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":"Engineering polymerases for applications in synthetic biology.","authors":"Ali Nikoomanzar,&nbsp;Nicholas Chim,&nbsp;Eric J Yik,&nbsp;John C Chaput","doi":"10.1017/S0033583520000050","DOIUrl":"https://doi.org/10.1017/S0033583520000050","url":null,"abstract":"<p><p>DNA polymerases play a central role in biology by transferring genetic information from one generation to the next during cell division. Harnessing the power of these enzymes in the laboratory has fueled an increase in biomedical applications that involve the synthesis, amplification, and sequencing of DNA. However, the high substrate specificity exhibited by most naturally occurring DNA polymerases often precludes their use in practical applications that require modified substrates. Moving beyond natural genetic polymers requires sophisticated enzyme-engineering technologies that can be used to direct the evolution of engineered polymerases that function with tailor-made activities. Such efforts are expected to uniquely drive emerging applications in synthetic biology by enabling the synthesis, replication, and evolution of synthetic genetic polymers with new physicochemical properties.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"53 ","pages":"e8"},"PeriodicalIF":6.1,"publicationDate":"2020-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583520000050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38195816","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":"Survival of the cheapest: how proteome cost minimization drives evolution.","authors":"Kasper P Kepp","doi":"10.1017/S0033583520000037","DOIUrl":"https://doi.org/10.1017/S0033583520000037","url":null,"abstract":"<p><p>Darwin's theory of evolution emphasized that positive selection of functional proficiency provides the fitness that ultimately determines the structure of life, a view that has dominated biochemical thinking of enzymes as perfectly optimized for their specific functions. The 20th-century modern synthesis, structural biology, and the central dogma explained the machinery of evolution, and nearly neutral theory explained how selection competes with random fixation dynamics that produce molecular clocks essential e.g. for dating evolutionary histories. However, quantitative proteomics revealed that selection pressures not relating to optimal function play much larger roles than previously thought, acting perhaps most importantly via protein expression levels. This paper first summarizes recent progress in the 21st century toward recovering this universal selection pressure. Then, the paper argues that proteome cost minimization is the dominant, underlying 'non-function' selection pressure controlling most of the evolution of already functionally adapted living systems. A theory of proteome cost minimization is described and argued to have consequences for understanding evolutionary trade-offs, aging, cancer, and neurodegenerative protein-misfolding diseases.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"53 ","pages":"e7"},"PeriodicalIF":6.1,"publicationDate":"2020-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583520000037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38117820","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":"Confined molecules: experiment meets theory in small spaces.","authors":"Yang Yu,&nbsp;Julius Rebek","doi":"10.1017/S0033583520000049","DOIUrl":"https://doi.org/10.1017/S0033583520000049","url":null,"abstract":"<p><p>The behavior of molecules confined to small spaces is fascinating chemistry and lies at the heart of signaling processes in biology. Our approach to confinement is through reversible encapsulation of small molecules in synthetic containers. We show that confinement leads to amplified reactivities in bimolecular reactions, stabilization of otherwise reactive species, and limitation in motions that create new stereochemical arrangements. The isolation of molecules from solvent makes for manageable computations and has stimulated theorist to examine reaction details in the limited space. Transition states for reactions and rearrangements can be calculated, the effects of (de)solvation can be evaluated and the magnetic properties of the containers can be compared with experimental observations. Finally, we outline several potential applications, including entanglement chemistry and the use of isomers in data storage.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"53 ","pages":"e6"},"PeriodicalIF":6.1,"publicationDate":"2020-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583520000049","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38117818","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":"Biophysical studies of protein misfolding and aggregation in <i>in vivo</i> models of Alzheimer's and Parkinson's diseases.","authors":"Tessa Sinnige,&nbsp;Karen Stroobants,&nbsp;Christopher M Dobson,&nbsp;Michele Vendruscolo","doi":"10.1017/S0033583520000025","DOIUrl":"https://doi.org/10.1017/S0033583520000025","url":null,"abstract":"<p><p>Neurodegenerative disorders, including Alzheimer's (AD) and Parkinson's diseases (PD), are characterised by the formation of aberrant assemblies of misfolded proteins. The discovery of disease-modifying drugs for these disorders is challenging, in part because we still have a limited understanding of their molecular origins. In this review, we discuss how biophysical approaches can help explain the formation of the aberrant conformational states of proteins whose neurotoxic effects underlie these diseases. We discuss in particular models based on the transgenic expression of amyloid-β (Aβ) and tau in AD, and α-synuclein in PD. Because biophysical methods have enabled an accurate quantification and a detailed understanding of the molecular mechanisms underlying protein misfolding and aggregation in vitro, we expect that the further development of these methods to probe directly the corresponding mechanisms in vivo will open effective routes for diagnostic and therapeutic interventions.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"49 ","pages":"e22"},"PeriodicalIF":6.1,"publicationDate":"2020-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583520000025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38005768","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":"Anionic food color tartrazine enhances antibacterial efficacy of histatin-derived peptide DHVAR4 by fine-tuning its membrane activity.","authors":"Maria Ricci,&nbsp;Kata Horváti,&nbsp;Tünde Juhász,&nbsp;Imola Szigyártó,&nbsp;György Török,&nbsp;Fanni Sebák,&nbsp;Andrea Bodor,&nbsp;László Homolya,&nbsp;Judit Henczkó,&nbsp;Bernadett Pályi,&nbsp;Tamás Mlinkó,&nbsp;Judith Mihály,&nbsp;Bilal Nizami,&nbsp;Zihuayuan Yang,&nbsp;Fengming Lin,&nbsp;Xiaolin Lu,&nbsp;Loránd Románszki,&nbsp;Attila Bóta,&nbsp;Zoltán Varga,&nbsp;Szilvia Bősze,&nbsp;Ferenc Zsila,&nbsp;Tamás Beke-Somfai","doi":"10.1017/S0033583520000013","DOIUrl":"https://doi.org/10.1017/S0033583520000013","url":null,"abstract":"<p><p>Here it is demonstrated how some anionic food additives commonly used in our diet, such as tartrazine (TZ), bind to DHVAR4, an antimicrobial peptide (AMP) derived from oral host defense peptides, resulting in significantly fostered toxic activity against both Gram-positive and Gram-negative bacteria, but not against mammalian cells. Biophysical studies on the DHVAR4-TZ interaction indicate that initially large, positively charged aggregates are formed, but in the presence of lipid bilayers, they rather associate with the membrane surface. In contrast to synergistic effects observed for mixed antibacterial compounds, this is a principally different mechanism, where TZ directly acts on the membrane-associated AMP promoting its biologically active helical conformation. Model vesicle studies show that compared to dye-free DHVAR4, peptide-TZ complexes are more prone to form H-bonds with the phosphate ester moiety of the bilayer head-group region resulting in more controlled bilayer fusion mechanism and concerted severe cell damage. AMPs are considered as promising compounds to combat formidable antibiotic-resistant bacterial infections; however, we know very little on their in vivo actions, especially on how they interact with other chemical agents. The current example illustrates how food dyes can modulate AMP activity, which is hoped to inspire improved therapies against microbial infections in the alimentary tract. Results also imply that the structure and function of natural AMPs could be manipulated by small compounds, which may also offer a new strategic concept for the future design of peptide-based antimicrobials.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"53 ","pages":"e5"},"PeriodicalIF":6.1,"publicationDate":"2020-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583520000013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37691195","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}