Quarterly Reviews of Biophysics最新文献

{"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}

{"title":"Chaperonin-assisted protein folding: a chronologue.","authors":"Arthur L Horwich,&nbsp;Wayne A Fenton","doi":"10.1017/S0033583519000143","DOIUrl":"https://doi.org/10.1017/S0033583519000143","url":null,"abstract":"<p><p>This chronologue seeks to document the discovery and development of an understanding of oligomeric ring protein assemblies known as chaperonins that assist protein folding in the cell. It provides detail regarding genetic, physiologic, biochemical, and biophysical studies of these ATP-utilizing machines from both in vivo and in vitro observations. The chronologue is organized into various topics of physiology and mechanism, for each of which a chronologic order is generally followed. The text is liberally illustrated to provide firsthand inspection of the key pieces of experimental data that propelled this field. Because of the length and depth of this piece, the use of the outline as a guide for selected reading is encouraged, but it should also be of help in pursuing the text in direct order.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"53 ","pages":"e4"},"PeriodicalIF":6.1,"publicationDate":"2020-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583519000143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37653783","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":"<i>De novo</i> protein design, a retrospective.","authors":"Ivan V Korendovych, William F DeGrado","doi":"10.1017/S0033583519000131","DOIUrl":"10.1017/S0033583519000131","url":null,"abstract":"<p><p>Proteins are molecular machines whose function depends on their ability to achieve complex folds with precisely defined structural and dynamic properties. The rational design of proteins from first-principles, or de novo, was once considered to be impossible, but today proteins with a variety of folds and functions have been realized. We review the evolution of the field from its earliest days, placing particular emphasis on how this endeavor has illuminated our understanding of the principles underlying the folding and function of natural proteins, and is informing the design of macromolecules with unprecedented structures and properties. An initial set of milestones in de novo protein design focused on the construction of sequences that folded in water and membranes to adopt folded conformations. The first proteins were designed from first-principles using very simple physical models. As computers became more powerful, the use of the rotamer approximation allowed one to discover amino acid sequences that stabilize the desired fold. As the crystallographic database of protein structures expanded in subsequent years, it became possible to construct proteins by assembling short backbone fragments that frequently recur in Nature. The second set of milestones in de novo design involves the discovery of complex functions. Proteins have been designed to bind a variety of metals, porphyrins, and other cofactors. The design of proteins that catalyze hydrolysis and oxygen-dependent reactions has progressed significantly. However, de novo design of catalysts for energetically demanding reactions, or even proteins that bind with high affinity and specificity to highly functionalized complex polar molecules remains an importnant challenge that is now being achieved. Finally, the protein design contributed significantly to our understanding of membrane protein folding and transport of ions across membranes. The area of membrane protein design, or more generally of biomimetic polymers that function in mixed or non-aqueous environments, is now becoming increasingly possible.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"53 ","pages":"e3"},"PeriodicalIF":6.1,"publicationDate":"2020-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243446/pdf/nihms-1581656.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37629365","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":"Osmosis.","authors":"A. Hill","doi":"10.32388/ok2cjg","DOIUrl":"https://doi.org/10.32388/ok2cjg","url":null,"abstract":"Book file PDF easily for everyone and every device. You can download and read online Osmosis file PDF Book only if you are registered here. And also you can download or read online all Book PDF file that related with Osmosis book. Happy reading Osmosis Bookeveryone. Download file Free Book PDF Osmosis at Complete PDF Library. This Book have some digital formats such us :paperbook, ebook, kindle, epub, fb2 and another formats. Here is The Complete PDF Book Library. It's free to register here to get Book file PDF Osmosis.","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"40 1","pages":"67-99"},"PeriodicalIF":6.1,"publicationDate":"2020-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86910515","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":"Off-pathway 3D-structure provides protection against spontaneous Asn/Asp isomerization: shielding proteins Achilles heel.","authors":"András Láng,&nbsp;Imre Jákli,&nbsp;Kata Nóra Enyedi,&nbsp;Gábor Mező,&nbsp;Dóra K Menyhárd,&nbsp;András Perczel","doi":"10.1017/S003358351900009X","DOIUrl":"https://doi.org/10.1017/S003358351900009X","url":null,"abstract":"<p><p>Spontaneous deamidation prompted backbone isomerization of Asn/Asp residues resulting in - most cases - the insertion of an extra methylene group into the backbone poses a threat to the structural integrity of proteins. Here we present a systematical analysis of how temperature, pH, presence of charged residues, but most importantly backbone conformation and dynamics affect isomerization rates as determined by nuclear magnetic resonance in the case of designed peptide-models. We demonstrate that restricted mobility (such as being part of a secondary structural element) may safeguard against isomerization, but this protective factor is most effective in the case of off-pathway folds which can slow the reaction by several magnitudes compared to their on-pathway counterparts. We show that the geometric descriptors of the initial nucleophilic attack of the isomerization can be used to classify local conformation and contribute to the design of stable protein drugs, antibodies or the assessment of the severity of mutations.</p><p><p>At any –Asn/AspGly– sites in proteins a spontaneous backbone isomerization occurs within days under physiological conditions leading to various forms of proteopathy. This unwanted transformation especially harmful to long-lived proteins (e.g. hemoglobin and crystallins), can be slowed down, though never stopped, by a rigid three-dimensional protein fold, if it can delay in the conformational maze, on-pathway intermediates from occurring.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"53 ","pages":"e2"},"PeriodicalIF":6.1,"publicationDate":"2020-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S003358351900009X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37594865","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":"<i>In cellulo</i> FRET-FLIM and single molecule tracking reveal the supra-molecular organization of the pyoverdine bio-synthetic enzymes in <i>Pseudomonas aeruginosa</i>.","authors":"Véronique Gasser,&nbsp;Morgane Malrieu,&nbsp;Anne Forster,&nbsp;Yves Mély,&nbsp;Isabelle J Schalk,&nbsp;Julien Godet","doi":"10.1017/S0033583519000155","DOIUrl":"https://doi.org/10.1017/S0033583519000155","url":null,"abstract":"<p><p>The bio-synthesis of pyoverdine (PVD) in Pseudomonas aeruginosa involves multiple enzymatic steps including the action of non-ribosomal peptide synthetases (NRPSs). One hallmark of NRPS is their ability to make usage of non-proteinogenic amino-acids synthesized by co-expressed accessory enzymes. It is generally proposed that different enzymes of a secondary metabolic pathway assemble into large supra-molecular complexes. However, evidence for the assembly of sequential enzymes in the cellular context is sparse. Here, we used in cellulo single-molecule tracking and Förster resonance energy transfer measured by fluorescence lifetime microscopy (FRET-FLIM) to explore the spatial partitioning of the ornithine hydroxylase PvdA and its interactions with NRPS. We found PvdA was mostly diffusing bound to large complexes in the cytoplasm with a small exchangeable trapped fraction. FRET-FLIM clearly showed that PvdA is physically interacting with PvdJ, PvdI, PvdL, and PvdD, the four NRPS involved in the PVD pathway in Pseudomonas aeruginosa PAO1. The binding modes of PvdA were strikingly different according to the NRPS it is interacting with, suggesting that PvdA binding sites have co-evolved with the enzymatic active sites of NRPS. Our data provide evidence for strongly organized multi-enzymatic complexes responsible for the bio-synthesis of PVD and illustrate how binding sites have evolved to finely control the co-localization of sequential enzymes and promote metabolic pathway efficiency.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"53 ","pages":"e1"},"PeriodicalIF":6.1,"publicationDate":"2020-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1017/S0033583519000155","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37523664","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":"Structure and function of the endothelial surface layer: unraveling the nanoarchitecture of biological surfaces","authors":"B. Reines, B. Ninham","doi":"10.1017/S0033583519000118","DOIUrl":"https://doi.org/10.1017/S0033583519000118","url":null,"abstract":"Abstract Among the unsolved mysteries of modern biology is the nature of a lining of blood vessels called the ‘endothelial surface layer’ or ESL. In venous micro-vessels, it is half a micron in thickness. The ESL is 10 times thicker than the endothelial glycocalyx (eGC) at its base, has been presumed to be comprised mainly of water, yet is rigid enough to exclude red blood cells. How is this possible? Developments in physical chemistry suggest that the venous ESL is actually comprised of nanobubbles of CO2, generated from tissue metabolism, in a foam nucleated in the eGC. For arteries, the ESL is dominated by nanobubbles of O2 and N2 from inspired air. The bubbles of the foam are separated and stabilized by thin layers of serum electrolyte and proteins, and a palisade of charged polymer strands of the eGC. The ESL seems to be a respiratory organ contiguous with the flowing blood, an extension of, and a ‘lung’ in miniature. This interpretation may have far-reaching consequences for physiology.","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"14 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2019-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81814957","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 biophysics of superoxide dismutase-1 and amyotrophic lateral sclerosis.","authors":"Gareth S A Wright, Svetlana V Antonyuk, S Samar Hasnain","doi":"10.1017/S003358351900012X","DOIUrl":"10.1017/S003358351900012X","url":null,"abstract":"<p><p>Few proteins have come under such intense scrutiny as superoxide dismutase-1 (SOD1). For almost a century, scientists have dissected its form, function and then later its malfunction in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). We now know SOD1 is a zinc and copper metalloenzyme that clears superoxide as part of our antioxidant defence and respiratory regulation systems. The possibility of reduced structural integrity was suggested by the first crystal structures of human SOD1 even before deleterious mutations in the sod1 gene were linked to the ALS. This concept evolved in the intervening years as an impressive array of biophysical studies examined the characteristics of mutant SOD1 in great detail. We now recognise how ALS-related mutations perturb the SOD1 maturation processes, reduce its ability to fold and reduce its thermal stability and half-life. Mutant SOD1 is therefore predisposed to monomerisation, non-canonical self-interactions, the formation of small misfolded oligomers and ultimately accumulation in the tell-tale insoluble inclusions found within the neurons of ALS patients. We have also seen that several post-translational modifications could push wild-type SOD1 down this toxic pathway. Recently we have come to view ALS as a prion-like disease where both the symptoms, and indeed SOD1 misfolding itself, are transmitted to neighbouring cells. This raises the possibility of intervention after the initial disease presentation. Several small-molecule and biologic-based strategies have been devised which directly target the SOD1 molecule to change the behaviour thought to be responsible for ALS. Here we provide a comprehensive review of the many biophysical advances that sculpted our view of SOD1 biology and the recent work that aims to apply this knowledge for therapeutic outcomes in ALS.</p>","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"56 1","pages":"e12"},"PeriodicalIF":7.2,"publicationDate":"2019-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76195250","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 behavior of ions in water is controlled by their water affinity","authors":"K. D. Collins","doi":"10.1017/S0033583519000106","DOIUrl":"https://doi.org/10.1017/S0033583519000106","url":null,"abstract":"Abstract The strong, long-range electrostatic forces described by Coulomb's law disappear for ions in water, and the behavior of these ions is instead controlled by their water affinity – a weak, short-range force which arises from their charge density. This was established experimentally in the mid-1980s by size-exclusion chromatography on carefully calibrated Sephadex® G-10 (which measures the effective volume and thus the water affinity of an ion) and by neutron diffraction with isotopic substitution (which measures the density and orientation of water molecules near the diffracting ion and thus its water affinity). These conclusions have been confirmed more recently by molecular dynamics simulations, which explicitly model each individual water molecule. This surprising change in force regime occurs because the oppositely charged ions in aqueous salt solutions exist functionally as ion pairs (separated by 0, 1 or 2 water molecules) as has now been shown by dielectric relaxation spectroscopy; this cancels out the strong long-range electrostatic forces and allows the weak, short-range water affinity effects to come to the fore. This microscopic structure of aqueous salt solutions is not captured by models utilizing a macroscopic dielectric constant. Additionally, the Law of Matching Water Affinity, first described in 1997 and 2004, establishes that contact ion pair formation is controlled by water affinity and is a major determinant of the solubility of charged species since only a net neutral species can change phases.","PeriodicalId":20828,"journal":{"name":"Quarterly Reviews of Biophysics","volume":"134 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2019-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77387029","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}