Quarterly Reviews of Biophysics最新文献

{"title":"Former QRB Editor Richard Henderson awarded the Nobel Prize.","authors":"Bengt Nordén, David Lilley","doi":"10.1017/S003358351800001X","DOIUrl":"https://doi.org/10.1017/S003358351800001X","url":null,"abstract":"","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"51 ","pages":"e2"},"PeriodicalIF":6.1,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S003358351800001X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37092598","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":"Solid and fluid segments within the same molecule of stratum corneum ceramide lipid.","authors":"Quoc Dat Pham,&nbsp;Enamul H Mojumdar,&nbsp;Gert S Gooris,&nbsp;Joke A Bouwstra,&nbsp;Emma Sparr,&nbsp;Daniel Topgaard","doi":"10.1017/S0033583518000069","DOIUrl":"https://doi.org/10.1017/S0033583518000069","url":null,"abstract":"<p><p>The outer layer of the skin, stratum corneum (SC) is an efficient transport barrier and it tolerates mechanical deformation. At physiological conditions, the majority of SC lipids are solid, while the presence of a small amount of fluid lipids is considered crucial for SC barrier and material properties. Here we use solid-state and diffusion nuclear magnetic resonance to characterize the composition and molecular dynamics of the fluid lipid fraction in SC model lipids, focusing on the role of the essential SC lipid CER EOS, which is a ceramide esterified omega-hydroxy sphingosine linoleate with very long chain. We show that both rigid and mobile structures are present within the same CER EOS molecule, and that the linoleate segments undergo fast isotropic reorientation while exhibiting extraordinarily slow self-diffusion. The characterization of this unusual self-assembly in SC lipids provides deepened insight into the molecular arrangement in the SC extracellular lipid matrix and the role of CER EOS linoleate in the healthy and diseased skin.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"51 ","pages":"e7"},"PeriodicalIF":6.1,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583518000069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37091134","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":"Thermodynamic, kinetic, and structural parameterization of human carbonic anhydrase interactions toward enhanced inhibitor design.","authors":"Vaida Linkuvienė,&nbsp;Asta Zubrienė,&nbsp;Elena Manakova,&nbsp;Vytautas Petrauskas,&nbsp;Lina Baranauskienė,&nbsp;Audrius Zakšauskas,&nbsp;Alexey Smirnov,&nbsp;Saulius Gražulis,&nbsp;John E Ladbury,&nbsp;Daumantas Matulis","doi":"10.1017/S0033583518000082","DOIUrl":"https://doi.org/10.1017/S0033583518000082","url":null,"abstract":"<p><p>The aim of rational drug design is to develop small molecules using a quantitative approach to optimize affinity. This should enhance the development of chemical compounds that would specifically, selectively, reversibly, and with high affinity interact with a target protein. It is not yet possible to develop such compounds using computational (i.e., in silico) approach and instead the lead molecules are discovered in high-throughput screening searches of large compound libraries. The main reason why in silico methods are not capable to deliver is our poor understanding of the compound structure-thermodynamics and structure-kinetics correlations. There is a need for databases of intrinsic binding parameters (e.g., the change upon binding in standard Gibbs energy (ΔGint), enthalpy (ΔHint), entropy (ΔSint), volume (ΔVintr), heat capacity (ΔCp,int), association rate (ka,int), and dissociation rate (kd,int)) between a series of closely related proteins and a chemically diverse, but pharmacophoric group-guided library of compounds together with the co-crystal structures that could help explain the structure-energetics correlations and rationally design novel compounds. Assembly of these data will facilitate attempts to provide correlations and train data for modeling of compound binding. Here, we report large datasets of the intrinsic thermodynamic and kinetic data including over 400 primary sulfonamide compound binding to a family of 12 catalytically active human carbonic anhydrases (CA). Thermodynamic parameters have been determined by the fluorescent thermal shift assay, isothermal titration calorimetry, and by the stopped-flow assay of the inhibition of enzymatic activity. Kinetic measurements were performed using surface plasmon resonance. Intrinsic thermodynamic and kinetic parameters of binding were determined by dissecting the binding-linked protonation reactions of the protein and sulfonamide. The compound structure-thermodynamics and kinetics correlations reported here helped to discover compounds that exhibited picomolar affinities, hour-long residence times, and million-fold selectivities over non-target CA isoforms. Drug-lead compounds are suggested for anticancer target CA IX and CA XII, antiglaucoma CA IV, antiobesity CA VA and CA VB, and other isoforms. Together with 85 X-ray crystallographic structures of 60 compounds bound to six CA isoforms, the database should be of help to continue developing the principles of rational target-based drug design.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"51 ","pages":"e10"},"PeriodicalIF":6.1,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583518000082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37092594","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":"DNA partitions into triplets under tension in the presence of organic cations, with sequence evolutionary age predicting the stability of the triplet phase - CORRIGENDUM.","authors":"Amirhossein Taghavi,&nbsp;Paul van der Schoot,&nbsp;Joshua T Berryman","doi":"10.1017/S0033583517000142","DOIUrl":"https://doi.org/10.1017/S0033583517000142","url":null,"abstract":"","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"51 ","pages":"e1"},"PeriodicalIF":6.1,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583517000142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35716971","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":"Secondary nucleation of monomers on fibril surface dominates α-synuclein aggregation and provides autocatalytic amyloid amplification.","authors":"Ricardo Gaspar,&nbsp;Georg Meisl,&nbsp;Alexander K Buell,&nbsp;Laurence Young,&nbsp;Clemens F Kaminski,&nbsp;Tuomas P J Knowles,&nbsp;Emma Sparr,&nbsp;Sara Linse","doi":"10.1017/S0033583516000172","DOIUrl":"https://doi.org/10.1017/S0033583516000172","url":null,"abstract":"<p><p>Parkinson's disease (PD) is characterized by proteinaceous aggregates named Lewy Bodies and Lewy Neurites containing α-synuclein fibrils. The underlying aggregation mechanism of this protein is dominated by a secondary process at mildly acidic pH, as in endosomes and other organelles. This effect manifests as a strong acceleration of the aggregation in the presence of seeds and a weak dependence of the aggregation rate on monomer concentration. The molecular mechanism underlying this process could be nucleation of monomers on fibril surfaces or fibril fragmentation. Here, we aim to distinguish between these mechanisms. The nature of the secondary processes was investigated using differential sedimentation analysis, trap and seed experiments, quartz crystal microbalance experiments and super-resolution microscopy. The results identify secondary nucleation of monomers on the fibril surface as the dominant secondary process leading to rapid generation of new aggregates, while no significant contribution from fragmentation was found. The newly generated oligomeric species quickly elongate to further serve as templates for secondary nucleation and this may have important implications in the spreading of PD.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"50 ","pages":"e6"},"PeriodicalIF":6.1,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583516000172","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35245190","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":"Lysozyme's lectin-like characteristics facilitates its immune defense function.","authors":"Ruiyan Zhang,&nbsp;Lisha Wu,&nbsp;Thomas Eckert,&nbsp;Monika Burg-Roderfeld,&nbsp;Miguel A Rojas-Macias,&nbsp;Thomas Lütteke,&nbsp;Vadim B Krylov,&nbsp;Dmitry A Argunov,&nbsp;Aritreyee Datta,&nbsp;Philipp Markart,&nbsp;Andreas Guenther,&nbsp;Bengt Norden,&nbsp;Roland Schauer,&nbsp;Anirban Bhunia,&nbsp;Mushira Abdelaziz Enani,&nbsp;Martin Billeter,&nbsp;Axel J Scheidig,&nbsp;Nikolay E Nifantiev,&nbsp;Hans-Christian Siebert","doi":"10.1017/S0033583517000075","DOIUrl":"https://doi.org/10.1017/S0033583517000075","url":null,"abstract":"<p><p>Interactions between human lysozyme (HL) and the lipopolysaccharide (LPS) of Klebsiella pneumoniae O1, a causative agent of lung infection, were identified by surface plasmon resonance. To characterize the molecular mechanism of this interaction, HL binding to synthetic disaccharides and tetrasaccharides representing one and two repeating units, respectively, of the O-chain of this LPS were studied. pH-dependent structural rearrangements of HL after interaction with the disaccharide were observed through nuclear magnetic resonance. The crystal structure of the HL-tetrasaccharide complex revealed carbohydrate chain packing into the A, B, C, and D binding sites of HL, which primarily occurred through residue-specific, direct or water-mediated hydrogen bonds and hydrophobic contacts. Overall, these results support a crucial role of the Glu35/Asp53/Trp63/Asp102 residues in HL binding to the tetrasaccharide. These observations suggest an unknown glycan-guided mechanism that underlies recognition of the bacterial cell wall by lysozyme and may complement the HL immune defense function.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"50 ","pages":"e9"},"PeriodicalIF":6.1,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583517000075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35245192","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":"Ribosome structural dynamics in translocation: yet another functional role for ribosomal RNA.","authors":"Harry F Noller,&nbsp;Laura Lancaster,&nbsp;Srividya Mohan,&nbsp;Jie Zhou","doi":"10.1017/S0033583517000117","DOIUrl":"https://doi.org/10.1017/S0033583517000117","url":null,"abstract":"<p><p>Ribosomes are remarkable ribonucleoprotein complexes that are responsible for protein synthesis in all forms of life. They polymerize polypeptide chains programmed by nucleotide sequences in messenger RNA in a mechanism mediated by transfer RNA. One of the most challenging problems in the ribosome field is to understand the mechanism of coupled translocation of mRNA and tRNA during the elongation phase of protein synthesis. In recent years, the results of structural, biophysical and biochemical studies have provided extensive evidence that translocation is based on the structural dynamics of the ribosome itself. Detailed structural analysis has shown that ribosome dynamics, like aminoacyl-tRNA selection and catalysis of peptide bond formation, is made possible by the properties of ribosomal RNA.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"50 ","pages":"e12"},"PeriodicalIF":6.1,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583517000117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35245130","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":"A new paradigm for atomically detailed simulations of kinetics in biophysical systems.","authors":"Ron Elber","doi":"10.1017/S0033583517000063","DOIUrl":"https://doi.org/10.1017/S0033583517000063","url":null,"abstract":"<p><p>The kinetics of biochemical and biophysical events determined the course of life processes and attracted considerable interest and research. For example, modeling of biological networks and cellular responses relies on the availability of information on rate coefficients. Atomically detailed simulations hold the promise of supplementing experimental data to obtain a more complete kinetic picture. However, simulations at biological time scales are challenging. Typical computer resources are insufficient to provide the ensemble of trajectories at the correct length that is required for straightforward calculations of time scales. In the last years, new technologies emerged that make atomically detailed simulations of rate coefficients possible. Instead of computing complete trajectories from reactants to products, these approaches launch a large number of short trajectories at different positions. Since the trajectories are short, they are computed trivially in parallel on modern computer architecture. The starting and termination positions of the short trajectories are chosen, following statistical mechanics theory, to enhance efficiency. These trajectories are analyzed. The analysis produces accurate estimates of time scales as long as hours. The theory of Milestoning that exploits the use of short trajectories is discussed, and several applications are described.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"50 ","pages":"e8"},"PeriodicalIF":6.1,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583517000063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35245191","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":"Chromatin-remodeling for transcription.","authors":"Yahli Lorch,&nbsp;Roger D Kornberg","doi":"10.1017/S003358351700004X","DOIUrl":"https://doi.org/10.1017/S003358351700004X","url":null,"abstract":"<p><p>The nucleosome serves as a general gene repressor, preventing all initiation of transcription except that which is brought about by specific positive regulatory mechanisms. The positive mechanisms begin with chromatin-remodeling by complexes that slide, disrupt, or otherwise alter the structure and organization of nucleosomes. RSC in yeast and its counterpart PBAF in human cells are the major remodeling complexes for transcription. RSC creates a nucleosome-free region in front of a gene, flanked by strongly positioned +1 and -1 nucleosomes, with the transcription start site typically 10-15 bp inside the border of the +1 nucleosome. RSC also binds stably to nucleosomes harboring regulatory elements and to +1 nucleosomes, perturbing their structures in a manner that partially exposes their DNA sequences. The cryo-electron microscope structure of a RSC-nucleosome complex reveals such a structural perturbation, with the DNA largely unwrapped from the nucleosome and likely interacting with a positively charged surface of RSC. Such unwrapping both exposes the DNA and enables its translocation across the histone octamer of the nucleosome by an ATP-dependent activity of RSC. Genetic studies have revealed additional roles of RSC in DNA repair, chromosome segregation, and other chromosomal DNA transactions. These functions of RSC likely involve the same fundamental activities, DNA unwrapping and DNA translocation.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"50 ","pages":"e5"},"PeriodicalIF":6.1,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S003358351700004X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35245189","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":"A stretched conformation of DNA with a biological role?","authors":"Niklas Bosaeus,&nbsp;Anna Reymer,&nbsp;Tamás Beke-Somfai,&nbsp;Tom Brown,&nbsp;Masayuki Takahashi,&nbsp;Pernilla Wittung-Stafshede,&nbsp;Sandra Rocha,&nbsp;Bengt Nordén","doi":"10.1017/S0033583517000099","DOIUrl":"https://doi.org/10.1017/S0033583517000099","url":null,"abstract":"<p><p>We have discovered a well-defined extended conformation of double-stranded DNA, which we call Σ-DNA, using laser-tweezers force-spectroscopy experiments. At a transition force corresponding to free energy change ΔG = 1·57 ± 0·12 kcal (mol base pair)-1 60 or 122 base-pair long synthetic GC-rich sequences, when pulled by the 3'-3' strands, undergo a sharp transition to the 1·52 ± 0·04 times longer Σ-DNA. Intriguingly, the same degree of extension is also found in DNA complexes with recombinase proteins, such as bacterial RecA and eukaryotic Rad51. Despite vital importance to all biological organisms for survival, genome maintenance and evolution, the recombination reaction is not yet understood at atomic level. We here propose that the structural distortion represented by Σ-DNA, which is thus physically inherent to the nucleic acid, is related to how recombination proteins mediate recognition of sequence homology and execute strand exchange. Our hypothesis is that a homogeneously stretched DNA undergoes a 'disproportionation' into an inhomogeneous Σ-form consisting of triplets of locally B-like perpendicularly stacked bases. This structure may ensure improved fidelity of base-pair recognition and promote rejection in case of mismatch during homologous recombination reaction. Because a triplet is the length of a gene codon, we speculate that the structural physics of nucleic acids may have biased the evolution of recombinase proteins to exploit triplet base stacks and also the genetic code.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"50 ","pages":"e11"},"PeriodicalIF":6.1,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583517000099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35245129","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}