BBA Advances最新文献

{"title":"Fibril core regions in engineered α-synuclein dimer are crucial for blocking of fibril elongation","authors":"Celina M. Schulz ,&nbsp;Anne Pfitzer ,&nbsp;Wolfgang Hoyer","doi":"10.1016/j.bbadva.2023.100110","DOIUrl":"https://doi.org/10.1016/j.bbadva.2023.100110","url":null,"abstract":"<div><p>Synucleinopathies like Parkinson's disease are neurodegenerative diseases which are associated with the deposition of fibrillar aggregates of the endogenous protein α-synuclein (α-syn). The inhibition of the elongation of α-syn fibrils is of great scientific interest and an option in the design of therapeutic strategies. Previously, we developed a disulfide-containing mutant of α-syn, called CC48, which inhibits fibril elongation by blocking of fibril ends. Surprisingly, wildtype (WT) α-syn molecules supported the blocked state, and a fusion of CC48 with WT α-syn, denoted WT-CC48, exhibited increased inhibitory potential. Here, we studied which regions of WT-CC48 are responsible for the strong inhibitory effect. To this end, we investigated a set of truncated versions of WT-CC48 by kinetic elongation assays, density gradient centrifugation, and atomic force microscopy. We show that in both the WT and the CC48 part of the fusion construct the hairpin region (residue 32–60) and NAC region (61–95), but not N- and C-terminal regions, are required for strong inhibition of fibril elongation. The required regions correspond to the segments forming the β-sheet core of α-syn fibrils. As α-syn fibrils typically consist of two protofilaments, the dimeric construct WT-CC48 provides the critical regions sufficient to cover the full β-sheetcore interface exposed at the fibril end, which can explain its high inhibitory efficiency. We suggest a mechanistic model of CC48-mediated inhibition of fibril elongation in which CC48 and WT α-syn cooperatively form an oligomer-like cap at the amyloid fibril end.</p></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"4 ","pages":"Article 100110"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266716032300039X/pdfft?md5=2948b6cb91e4d54a8f75ea2db8f29ffa&pid=1-s2.0-S266716032300039X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134653737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homeostasis of carbohydrates and reactive oxygen species is critically changed in the brain of middle-aged mice: Molecular mechanisms and functional reasons","authors":"Maria M. Bayliak ,&nbsp;Dmytro V. Gospodaryov ,&nbsp;Volodymyr I. Lushchak","doi":"10.1016/j.bbadva.2023.100077","DOIUrl":"10.1016/j.bbadva.2023.100077","url":null,"abstract":"<div><p>The brain is an organ that consumes a lot of energy. In the brain, energy is required for synaptic transmission, numerous biosynthetic processes and axonal transport in neurons, and for many supportive functions of glial cells. The main source of energy in the brain is glucose and to a lesser extent lactate and ketone bodies. ATP is formed at glucose catabolism via glycolysis and oxidative phosphorylation in mitochondrial electron transport chain (ETC) within mitochondria being the main source of ATP. With age, brain's energy metabolism is disturbed, involving a decrease in glycolysis and mitochondrial dysfunction. The latter is accompanied by intensified generation of reactive oxygen species (ROS) in ETC leading to oxidative stress. Recently, we have found that crucial changes in energy metabolism and intensity of oxidative stress in the mouse brain occur in middle age with minor progression in old age. In this review, we analyze the metabolic changes and functional causes that lead to these changes in the aging brain.</p></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"3 ","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10074963/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9385045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A few notes on science in Ukraine","authors":"Anna V. El'skaya","doi":"10.1016/j.bbadva.2023.100089","DOIUrl":"10.1016/j.bbadva.2023.100089","url":null,"abstract":"<div><p>As a person who has had a long scientific career in Ukraine, both before and after its re-acquisition of independence thirty years ago, I would like to share my observations with the readership of this Special Issue. By no means are these observations meant to provide a systematic presentation, which requires a different format. Rather, they are highly personal notes, providing snippets of the past and present and a discussion of the future of Ukrainian science. They also allow me to acknowledge my wonderful colleagues and bright students. I am delighted to see that many of them have contributed excellent reviews and original manuscripts to this Special Issue. (I am also keenly aware of the fact that because of the brutal invasion and bombardments by our imperial neighbor, many of my colleagues have been unable to share their latest work). It will be up to this next generation of Ukrainian scientists to develop Biological Sciences in Ukraine in the future.</p></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"3 ","pages":"Article 100089"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10123332/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9356003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OPINION: History and Perspectives of ASICs","authors":"Oleg Krishtal","doi":"10.1016/j.bbadva.2023.100087","DOIUrl":"10.1016/j.bbadva.2023.100087","url":null,"abstract":"<div><p>The author recalls several particularly memorable events during his scientific career that led to the discovery of acid-sensing ion channels and ionotropic purinergic receptors. The readers learn of the events of 1975 when the first intracellular perfusion of the neuronal soma has been achieved- the event that led to the precise measurement of the calcium currents through the neuronal plasma membrane. Next, 1980 brings us to the functional discovery of the neuronal proton receptors found in mammalian sensory neurons. The molecular identity of these receptors was discovered in the lab of Dr. M. Lazdunsky and they were named acid-sensing ion channels or ASICs. Now it is clear that every mammalian neuron expresses at least one member of the ASICs family. And yet, ASICs are known for their functional diversity which is currently being studied extensively due to their prominence as pharmacological targets. Eventually, readers learn of the events of 1983 and the functional discovery of ionotropic purinergic receptors, and their molecular identification in the lab of Dr. R.A. North that coined the name of P2X ionotropic receptors.</p></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"3 ","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10291021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9726378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ukrainian science in the context of its anticolonial struggle","authors":"Alexey S. Ladokhin","doi":"10.1016/j.bbadva.2023.100093","DOIUrl":"10.1016/j.bbadva.2023.100093","url":null,"abstract":"<div><p>The current Special Issue entitled “Highlights of Ukrainian Molecular Biosciences” is dedicated to presenting recent contributions in the areas of biochemistry and biophysics, molecular biology and genetics, molecular and cellular physiology, and physical chemistry of biological macromolecules made by researchers either currently working in Ukraine or those who have obtained their training in Ukrainian institutions. Obviously, such a collection can present only a small sample of relevant studies, making the editorial task a particular challenge, as inevitably many deserving research groups were missed. In addition, we are greatly sorrowed that some of the invitees were unable to contribute due to the continued bombardments and military attacks perpetrated by Russia in Ukraine since 2014, and especially in 2022. This Introduction is also intended to provide a broader context for understanding of Ukraine's decolonization struggle, both in science and on the battlefield, and outlines suggestions for the global scientific community.</p></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"3 ","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9b/25/main.PMC10275747.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9654903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of two bacterial multi-flavinylated proteins harboring multiple covalent flavin cofactors","authors":"Yapei Tong,&nbsp;Henriette J. Rozeboom,&nbsp;Marnix R. Loonstra,&nbsp;Hein J. Wijma,&nbsp;Marco W. Fraaije","doi":"10.1016/j.bbadva.2023.100097","DOIUrl":"10.1016/j.bbadva.2023.100097","url":null,"abstract":"<div><p>In recent years, studies have shown that a large number of bacteria secrete multi-flavinylated proteins. The exact roles and properties, of these extracellular flavoproteins that contain multiple covalently anchored FMN cofactors, are still largely unknown. Herein, we describe the biochemical and structural characterization of two multi-FMN-containing covalent flavoproteins, SaFMN3 from <em>Streptomyces azureus</em> and CbFMN4 from <em>Clostridiaceae bacterium</em>. Based on their primary structure, these proteins were predicted to contain three and four covalently tethered FMN cofactors, respectively. The genes encoding SaFMN3 and CbFMN4 were heterologously coexpressed with a flavin transferase (ApbE) in <em>Escherichia coli</em>, and could be purified by affinity chromatography in good yields. Both proteins were found to be soluble and to contain covalently bound FMN molecules. The SaFMN3 protein was studied in more detail and found to display a single redox potential (-184 mV) while harboring three covalently attached flavins. This is in line with the high sequence similarity when the domains of each flavoprotein are compared. The fully reduced form of SaFMN3 is able to use dioxygen as electron acceptor. Single domains from both proteins were expressed, purified and crystallized. The crystal structures were elucidated, which confirmed that the flavin cofactor is covalently attached to a threonine. Comparison of both crystal structures revealed a high similarity, even in the flavin binding pocket. Based on the crystal structure, mutants of the SaFMN3-D2 domain were designed to improve its fluorescence quantum yield by changing the microenvironment of the isoalloxazine moiety of the flavin cofactor. Residues that quench the flavin fluorescence were successfully identified. Our study reveals biochemical details of multi-FMN-containing proteins, contributing to a better understanding of their role in bacteria and providing leads to future utilization of these flavoprotein in biotechnology.</p></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"4 ","pages":"Article 100097"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10339131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10200640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photobuforin II, a fluorescent photoswitchable peptide","authors":"Cristina R. Ventura,&nbsp;Gregory R. Wiedman","doi":"10.1016/j.bbadva.2023.100106","DOIUrl":"10.1016/j.bbadva.2023.100106","url":null,"abstract":"<div><p>Antimicrobial peptide buforin II translocates across the cell membrane and binds to DNA. Its sequence is identical to a portion of core histone protein H2A making it a highly charged peptide. Buforin II has a proline residue in the middle of its sequence that creates a helix-hinge-helix motif which has been found to play a key role in its ability to translocate across the cell membrane. To explore the structure-function relationship of this proline residue this study has replaced P11 with a meta-substituted azobenzene amino acid (Z). The resultant peptide, photobuforin II, retained the secondary structure and membrane activity of the naturally occurring peptide while gaining new spectroscopic properties. Photobuforin II can be isomerized from its <em>trans</em> to <em>cis</em> isomer upon irradiation with ultra-violet (UV) light and from its cis to trans isomer upon irradiation with visible (VL). Photobuforin II is also fluorescent with an emission peak at 390 nm. The intrinsic fluorescence of the peptide was used to determine binding to the membrane and to DNA. VL-treated photobuforin II has a 2-fold lower binding constant compared to UV-treated photobuforin and causes 11-fold more membrane leakage in 3:1 POPC:POPG vesicles. Photobuforin II provides insights into the importance of structure function relationships in membrane active peptides while also demonstrating that azobenzene can be used in certain peptide sequences to produce intrinsic fluorescence.</p></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"4 ","pages":"Article 100106"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41239384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transport limited adsorption experiments give a new lower estimate of the turnover frequency of Escherichia coli hydrogenase 1","authors":"Anna Aldinio-Colbachini,&nbsp;Andrea Fasano,&nbsp;Chloé Guendon,&nbsp;Aurore Jacq-Bailly,&nbsp;Jérémy Wozniak,&nbsp;Carole Baffert,&nbsp;Arlette Kpebe,&nbsp;Christophe Léger,&nbsp;Myriam Brugna,&nbsp;Vincent Fourmond","doi":"10.1016/j.bbadva.2023.100090","DOIUrl":"https://doi.org/10.1016/j.bbadva.2023.100090","url":null,"abstract":"<div><p>Protein Film Electrochemistry is a technique in which a redox enzyme is directly wired to an electrode, which substitutes for the natural redox partner. In this technique, the electrical current flowing through the electrode is proportional to the catalytic activity of the enzyme. However, in most cases, the amount of enzyme molecules contributing to the current is unknown and the absolute turnover frequency cannot be determined. Here, we observe the formation of electrocatalytically active films of <em>E. coli</em> hydrogenase 1 by rotating an electrode in a sub-nanomolar solution of enzyme. This process is slow, and we show that it is mass-transport limited. Measuring the rate of the immobilization allows the determination of an estimation of the turnover rate of the enzyme, which appears to be much greater than that deduced from solution assays under the same conditions.</p></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"3 ","pages":"Article 100090"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49775951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Five questions on how biochemistry can combat climate change","authors":"Kevin Chen,&nbsp;Yaya Guo,&nbsp;Kenneth How,&nbsp;Arianny Acosta,&nbsp;Diane Documet,&nbsp;Cathleen Liang,&nbsp;Deborah Arul,&nbsp;Sasha Wood,&nbsp;Katherine Moon,&nbsp;Lilijana S. Oliver,&nbsp;Emely Lopez Fajardo,&nbsp;Miriam Kopyto,&nbsp;Morgan Shine,&nbsp;Karla M Neugebauer","doi":"10.1016/j.bbadva.2023.100111","DOIUrl":"https://doi.org/10.1016/j.bbadva.2023.100111","url":null,"abstract":"<div><p>Global warming is caused by human activity, such as the burning of fossil fuels, which produces high levels of greenhouse gasses. As a consequence, climate change impacts all organisms and the greater ecosystem through changing conditions from weather patterns to the temperature, pH and salt concentrations found in waterways and soil. These environmental changes fundamentally alter many parameters of the living world, from the kinetics of chemical reactions and cellular signaling pathways to the accumulation of unforeseen chemicals in the environment, the appearance and dispersal of new diseases, and the availability of traditional foods. Some organisms adapt to extremes, while others cannot. This article asks five questions that prompt us to consider the foundational knowledge that biochemistry can bring to the table as we meet the challenge of climate change. We approach climate change from the molecular point of view, identifying how cells and organisms – from microbes to plants and animals – respond to changing environmental conditions. To embrace the concept of “one health” for all life on the planet, we argue that we must leverage biochemistry, cell biology, molecular biophysics and genetics to fully understand the impact of climate change on the living world and to bring positive change.</p></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"4 ","pages":"Article 100111"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667160323000406/pdfft?md5=6b84e5b30f866d85f5c97a7563505c68&pid=1-s2.0-S2667160323000406-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138413130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rationally designed molecularly imprinted polymer membranes as antibody and enzyme mimics in analytical biotechnology.","authors":"T. Sergeyeva, O. Piletska, S. Piletsky","doi":"10.2139/ssrn.4274676","DOIUrl":"https://doi.org/10.2139/ssrn.4274676","url":null,"abstract":"The paper is a self-review of works on development of new approaches to formation of mimics of receptor and catalytic sites of biological macromolecules in the structure of highly cross-linked polymer membranes and thin films. The general strategy for formation of the binding sites in molecularly imprinted polymer (MIP) membranes and thin films was described. A selective recognition of a number of food toxins, endocrine disruptors and metabolites is based on the results of computational modeling data for the prediction and optimization of their structure. A strategy proposed for the design of the artificial binding sites in MIP membranes was supported by the research performed by the authors on development of a number of the MIP membrane-based affinity and catalytic biosensors for selective and sensitive measurement (detection limits 0.3-100 nM) of the target analytes. Novel versatile approaches aimed at improving sensitivity of the developed biosensor systems were discussed.","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"3 1","pages":"100070"},"PeriodicalIF":0.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47330368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}