European Biophysics Journal最新文献

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Modulation of conformational features and oligomerization of MMACHC by cobalamin variants: impact of the R161Q mutation in cblC disease. 钴胺素变异对MMACHC构象特征和寡聚化的调节:R161Q突变对cblC疾病的影响
IF 2.2 4区 生物学
European Biophysics Journal Pub Date : 2025-06-27 DOI: 10.1007/s00249-025-01777-5
Lisa Longo, Maria Assunta Costa, Rita Carrotta, Maria Rosalia Mangione, Vincenzo Martorana, Marco Tutone, Maria Grazia Ortore, Paula M Garcia-Franco, Sonia Vega, Adrian Velazquez-Campoy, Rosa Passantino, Silvia Vilasi
{"title":"Modulation of conformational features and oligomerization of MMACHC by cobalamin variants: impact of the R161Q mutation in cblC disease.","authors":"Lisa Longo, Maria Assunta Costa, Rita Carrotta, Maria Rosalia Mangione, Vincenzo Martorana, Marco Tutone, Maria Grazia Ortore, Paula M Garcia-Franco, Sonia Vega, Adrian Velazquez-Campoy, Rosa Passantino, Silvia Vilasi","doi":"10.1007/s00249-025-01777-5","DOIUrl":"https://doi.org/10.1007/s00249-025-01777-5","url":null,"abstract":"<p><p>Vitamin B12 (cobalamin, Cbl) is a coordination compound of the cobalt, located at the center of a corrin ring composed of four pyrrolic-like groups. The cobalt ion can be bound to a variety of upper axial ligands, which vary among different cobalamin forms, including hydroxocobalamin (OHCbl), cyanocobalamin (CNCbl), methylcobalamin (MeCbl), and adenosylcobalamin (AdoCbl). MeCbl and AdoCbl are considered the biologically active forms, serving as cofactors in the metabolism of methylmalonic acid (MMA) and homocysteine (HCY). Impaired conversion of these metabolites leads to their pathological accumulation, resulting in severe cellular damage. This is precisely what occurs in cblC deficiency, a rare inborn disorder caused by mutations in the MMACHC protein, which plays a crucial role in binding and processing the various cobalamin forms. Mutations affecting MMACHC function impair its ability to correctly handle cobalamins, leading to the disease. In this study, we evaluated the impact of various cobalamin forms, specifically AdoCbl, MeCbl, and CNCbl, on the stability and oligomeric organization of the wild type MMACHC protein, using circular dichroism spectroscopy, native gel electrophoresis, and small-angle X-ray scattering. Moreover, isothermal titration calorimetry experiments provided insights into the thermodynamic parameters governing MMACHC binding to these cobalamins. In addition, we also assessed how the R161Q mutation in MMACHC alters the affinity of this protein for the different vitamin B12 forms, leading to decreased stability and impaired homodimerization, a process likely relevant to its functional role. Our findings provide molecular insights into cblC pathogenesis and advance our understanding of MMACHC structure-function relationships.</p>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inside the membrane: a closer look using elastic scattering techniques and friends. 薄膜内部:使用弹性散射技术和朋友更近距离观察。
IF 2.2 4区 生物学
European Biophysics Journal Pub Date : 2025-06-26 DOI: 10.1007/s00249-025-01761-z
Michael Kaltenegger, Enrico F Semeraro, Georg Pabst
{"title":"Inside the membrane: a closer look using elastic scattering techniques and friends.","authors":"Michael Kaltenegger, Enrico F Semeraro, Georg Pabst","doi":"10.1007/s00249-025-01761-z","DOIUrl":"https://doi.org/10.1007/s00249-025-01761-z","url":null,"abstract":"<p><p>Biological membranes are highly dynamic and adaptive interfaces that define cellular compartments, posing significant challenges for detailed characterization. Among the diverse range of experimental and computational techniques, small-angle scattering emerges as a label-free, non-invasive method capable of probing membrane structures across length scales from micrometers to subnanometers. By exploiting the complementary contrasts of X-ray and neutron scattering, combined with advanced optimization algorithms, this approach has provided unique insights into membranes with well-defined lipid and protein architectures. In this review, we highlight recent studies from the Pabst Lab, including investigations of lipid domains, asymmetric lipid membranes, and intrinsic lipid curvature. Furthermore, we explore the functional implications of these findings, such as the activity of an integral membrane enzyme and the effects of antimicrobial peptides in live cells. These examples underscore the versatility of small-angle scattering techniques in elucidating membrane functions, offering valuable perspectives for understanding cellular processes and advancing pharmaceutical applications.</p>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Physical principles underpinning molecular-level protein evolution. 支撑分子水平蛋白质进化的物理原理。
IF 2.2 4区 生物学
European Biophysics Journal Pub Date : 2025-06-26 DOI: 10.1007/s00249-025-01776-6
Jorge A Vila
{"title":"Physical principles underpinning molecular-level protein evolution.","authors":"Jorge A Vila","doi":"10.1007/s00249-025-01776-6","DOIUrl":"https://doi.org/10.1007/s00249-025-01776-6","url":null,"abstract":"<p><p>Since protein mutations are the main driving force of evolution at a molecular level, a proper analysis of the factors controlling them-such as the proteins' robustness, the evolutionary pathways, the number of ancestors, the epistasis, the post-translational modifications, and the location and the order of mutations-will enable us to find a response to several crucial queries in evolutionary biology. Among them, we highlight the following: At the molecular level, what factors determine whether protein evolution is repeatable? Aiming at finding an answer to this and several other significant questions behind protein evolvability, we distinguish two evolutionary models in our analysis: convergent and divergent, based on whether or not a \"target sequence\" needs to be reached after n mutational steps beginning with a wild-type protein sequence (from an unknown ancestor). Preliminary results suggest-regardless of whether the evolution is convergent or divergent-a tight relationship between the thermodynamic hypothesis (or Anfinsen's dogma) and the protein evolution at the molecular level. This conjecture will allow us to uncover how fundamental physical principles guide protein evolution and to gain a deeper grasp of mutationally driven evolutionary processes and the factors that influence them. Breaking down complex evolutionary problems into manageable pieces-without compromising the vision of the problem as a whole-could lead to effective solutions to critical evolutionary biology challenges, paving the way for further progress in this field.</p>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Quadruplexes with a grain of salt: influence of cation type and concentration on DNA G4 stability. 带盐颗粒的四联体:阳离子类型和浓度对DNA G4稳定性的影响。
IF 2.2 4区 生物学
European Biophysics Journal Pub Date : 2025-06-25 DOI: 10.1007/s00249-025-01772-w
Anne Cucchiarini, Filip Kledus, Yu Luo, Václav Brázda, Jean-Louis Mergny
{"title":"Quadruplexes with a grain of salt: influence of cation type and concentration on DNA G4 stability.","authors":"Anne Cucchiarini, Filip Kledus, Yu Luo, Václav Brázda, Jean-Louis Mergny","doi":"10.1007/s00249-025-01772-w","DOIUrl":"https://doi.org/10.1007/s00249-025-01772-w","url":null,"abstract":"<p><p>G-quadruplexes (G4) are stabilized by intra-quartet hydrogen bonds stacking between quartets, as well as specific and non-specific ionic interactions. Cation effects on G-quadruplexes differ significantly from those on duplexes, and specific cation coordination is indeed required to stabilize G4 structures. Most studies so far involve \"standard\" concentrations of potassium or sodium cations because of their prevalence in human cells, but several other monovalent and divalent cations may promote quadruplex formation. In addition, ionic strength may be different in other organisms such as Halophiles: the intracellular cation (potassium) concentration in salt-loving organisms such as Haloferax volcanii can be extremely high. In this study, we first performed a bioinformatics analysis of G4 propensity in halophiles and analyzed the impact of altering ionic strength or ionic balance on G4 or hairpin duplex stability. We then present a detailed and quantitative assessment of salt effect on a variety of duplex and quadruplex sequences. Over a dozen different quadruplex and duplex sequences were investigated by FRET melting and UV melting experiments. In addition, changes in sodium/potassium balance possibly occurring in human cells have a modest effect on G4-duplex competition. We also confirm that lithium is rather a \"G4-indifferent\" than a G4-destabilizing cation.</p>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Professor Emil Paleček: seven decades with electrodes and biomolecules at the Institute of Biophysics of the CAS. Emil paleek教授:在中国科学院生物物理研究所从事电极和生物分子研究70年。
IF 2.2 4区 生物学
European Biophysics Journal Pub Date : 2025-06-25 DOI: 10.1007/s00249-025-01771-x
Miroslav Fojta, Jan Paleček
{"title":"Professor Emil Paleček: seven decades with electrodes and biomolecules at the Institute of Biophysics of the CAS.","authors":"Miroslav Fojta, Jan Paleček","doi":"10.1007/s00249-025-01771-x","DOIUrl":"https://doi.org/10.1007/s00249-025-01771-x","url":null,"abstract":"<p><p>This year we celebrate seventy years since the establishment of the Institute of Biophysics of the Czechoslovak Academy of Sciences (IBP) (founded on January 1, 1955). If we look into the biography of Professor Emil Paleček (born on October 3, 1930), one of the most world-recognized personalities associated with the Institute and one of the most cited Czech scientists, known as the founder of nucleic acids electrochemistry, we are drawn to the same year, i.e. 1955, as the year in which Emil Paleček finished his studies in biochemistry and joined the IBP, where he worked with admirable vitality, enthusiasm and dedication until his death (October 30, 2018). In the context of celebration of founding of the Institute, we would like to commemorate in this article a personality who significantly influenced the history of the Institute alongside the important discoveries and research directions that defined his extremely successful career. We prefer this form, which is a sort of a mini-review of the most important results of the laboratory obtained under EP's leadership over 63 years, presented in mutual context and natural relations. For his life's work, Professor Paleček received many prestigious awards, with the Czech Head Award in 2014 and the Neuron Foundation Award in 2017 being the most distinguished.</p>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Image analysis tools for improved characterization of nuclear chromatin patterns by confocal fluorescence microscopy. 通过共聚焦荧光显微镜改进核染色质模式表征的图像分析工具。
IF 2.2 4区 生物学
European Biophysics Journal Pub Date : 2025-06-23 DOI: 10.1007/s00249-025-01770-y
Mohammadmehdi Roushenas, Marco Salerno, Virginia Bazzurro, Elena Gatta, Alberto Diaspro
{"title":"Image analysis tools for improved characterization of nuclear chromatin patterns by confocal fluorescence microscopy.","authors":"Mohammadmehdi Roushenas, Marco Salerno, Virginia Bazzurro, Elena Gatta, Alberto Diaspro","doi":"10.1007/s00249-025-01770-y","DOIUrl":"https://doi.org/10.1007/s00249-025-01770-y","url":null,"abstract":"<p><p>We have collected fluorescence images of fixed cell nuclei of two different types-HeLa and HepG2-with DNA labeled by a standard fluorophore, and have devised three different quantitative parameters aimed to describe the distribution of the nuclear chromatin. The parameters are the fractal dimension, associated with the intricacy and hierarchical structure of chromatin; the total perimeter of local maxima, associated with the amount of chromatin domains; and the radial distance of angularly averaged intensity profile maximum, associated with the possible occurrence of a peak density at a characteristic distance from the nucleus center. Our results suggested that it was possible to differentiate the two types of cells in the 3D space of the defined parameters. Therefore, these parameters appear promising in identifying specific functional patterns in chromatin. At the same time, the negative control of different runs of measurements on the same cell type also showed at least partial differentiation. Thus, the tool proposed here for nuclear chromatin pattern characterization is probably sensitive to the cell life cycle moment almost as much as to the cell type and should be tested further on cells synchronized at the same phase during their cycle.</p>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fragmentation of nucleoli in senescent cancer cells is associated with increased levels of polyadenylated transcripts derived from noncoding regions of rDNA units. 衰老癌细胞核仁的断裂与rDNA非编码区衍生的多腺苷化转录物水平的增加有关。
IF 2.2 4区 生物学
European Biophysics Journal Pub Date : 2025-06-23 DOI: 10.1007/s00249-025-01773-9
Jana Sochorová, Emilie Lukášová, Eva Volfová Polanská, Kateřina Řehůřková, Aleš Kovařík
{"title":"Fragmentation of nucleoli in senescent cancer cells is associated with increased levels of polyadenylated transcripts derived from noncoding regions of rDNA units.","authors":"Jana Sochorová, Emilie Lukášová, Eva Volfová Polanská, Kateřina Řehůřková, Aleš Kovařík","doi":"10.1007/s00249-025-01773-9","DOIUrl":"https://doi.org/10.1007/s00249-025-01773-9","url":null,"abstract":"<p><p>In this study, we investigated the behavior of rDNA loci in senescent MCF-7 mammary cancer cells induced by gamma irradiation. To analyze changes in nucleolar structure we used rDNA-FISH and immunohistochemical staining with fibrillarin and UBF transcription factor. The expression levels of rDNAs and nucleolar proteins were determined by RNA-seq of total and poly-A libraries. The cytological and molecular parameters of nucleoli were monitored throughout the 7-day interval following irradiation. Senescent cells exhibited a higher proportion of smaller nucleoli as compared to cycling cells, indicating nucleolar fragmentation. The rDNA copy number and expression of rDNA variants remained stable in cycling and senescent cells. However, the levels of polyadenylated rRNA species derived from external (5'ETS) and internal (ITS1) rDNA spacers tend to increase (c.2 fold) following irradiation. At the protein level, senescent cells showed decreased levels of fibrillarin and UBF transcription factor while localization of both proteins in the nucleolus was not impaired. We conclude that withdrawal from cell cycle does not change expression patterns of rDNA variants. However, defects in rRNA processing may lead to fragmentation of nucleoli in senescent cells.</p>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Uptake of gold nanoparticles in HeLa cells observed by confocal microscopy shows dependency on particle size and shape. 通过共聚焦显微镜观察,HeLa细胞对金纳米颗粒的吸收与颗粒大小和形状有关。
IF 2.2 4区 生物学
European Biophysics Journal Pub Date : 2025-06-19 DOI: 10.1007/s00249-025-01769-5
Kimiya Pakravanan, Virginia Bazzurro, Marco Salerno, Alberto Diaspro
{"title":"Uptake of gold nanoparticles in HeLa cells observed by confocal microscopy shows dependency on particle size and shape.","authors":"Kimiya Pakravanan, Virginia Bazzurro, Marco Salerno, Alberto Diaspro","doi":"10.1007/s00249-025-01769-5","DOIUrl":"10.1007/s00249-025-01769-5","url":null,"abstract":"<p><p>Uptake of gold nanoparticles by HeLa cells fixed at different incubation times of up to eight hours was investigated using 3D confocal laser scanning microscopy followed by image analysis. The cell bodies were characterized by fluorescence labeling, whereas the gold nanoparticles were identified by light scattering. The amount of nanoparticles uptaken at different times was evaluated with Fiji according to a dedicated protocol. We assessed the effect of particle size (80 and 150 nm diameter spheres) and shape (spheres vs \"urchins\") on their uptake. The large spherical nanoparticles presented approximately fourfold higher levels of uptake than the nanourchins. Also, the spheres presented a clearly increasing uptake in the time profile, reaching a maximum around seven hours and then showing a slight decrease. We ascribe this behavior to a lower aptitude of the cells for taking up nanoparticles with either urchin shape or smaller size and to the possible presence of competing kinetics for exocytosis at the longest times. Live experiments confirmed for the time profile a relatively flat cell response to the urchins and an increasing response to the spheres, yet with a final plateau. However, in the live case, the internalization levels were as low for the spheres as for the urchins.</p>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biophysical and microbiological aspects of the interaction between Yersinia pestis PsaA and bacteriophage L-413C. 鼠疫耶尔森菌PsaA与噬菌体L-413C相互作用的生物物理和微生物学方面的研究。
IF 2.2 4区 生物学
European Biophysics Journal Pub Date : 2025-06-16 DOI: 10.1007/s00249-025-01768-6
Ilya Konyshev, Lyubov Dudina, Vladislav Belozerov, Sergey Ivanov, Svetlana Dentovskaya, Andrey Anisimov, Andrey Byvalov
{"title":"Biophysical and microbiological aspects of the interaction between Yersinia pestis PsaA and bacteriophage L-413C.","authors":"Ilya Konyshev, Lyubov Dudina, Vladislav Belozerov, Sergey Ivanov, Svetlana Dentovskaya, Andrey Anisimov, Andrey Byvalov","doi":"10.1007/s00249-025-01768-6","DOIUrl":"https://doi.org/10.1007/s00249-025-01768-6","url":null,"abstract":"<p><p>There has been a great interest in developing the phage-containing remedy against plague caused by antimicrobial resistant strains of Yersinia pestis, which have been increasingly isolated in recent years from sick humans and animals. Studies thus are under way to develop a \"phage cocktail\", which is expected to be effective against a wide range of pathogenic strains. Our paper sheds light on the role of Y. pestis antigen PsaA in reception of the phage L-413C, which might be a possible component of such a \"cocktail\". Using optical trapping (OT) and atomic force microscopy (AFM), we showed that PsaA-positive cells and PsaA-coated beads or cantilevers bound more effectively to a substrate coated with L-413C rather than Pokrovskaya phage. Comparing two isogenic strains of Y. pestis (EV and EV∆psaA), we found that when bacteria and phages are co-incubated under slightly acidic pH, as if in a eukaryotic cell, PsaA-positive cells bound the phage L-413C more effectively. There is good evidence to say that L-413C may become a component of a new anti-plague therapy due to its high ability to interact with the pili-forming protein PsaA from the outer membrane of Y. pestis.</p>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144309396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structural adaptability of SARS-CoV-2 Nsp1 with the host network. SARS-CoV-2 Nsp1与主机网络的结构适应性
IF 2.2 4区 生物学
European Biophysics Journal Pub Date : 2025-06-14 DOI: 10.1007/s00249-025-01762-y
Monikaben Padariya, Ted Hupp, Umesh Kalathiya
{"title":"Structural adaptability of SARS-CoV-2 Nsp1 with the host network.","authors":"Monikaben Padariya, Ted Hupp, Umesh Kalathiya","doi":"10.1007/s00249-025-01762-y","DOIUrl":"https://doi.org/10.1007/s00249-025-01762-y","url":null,"abstract":"<p><p>The SARS-CoV-2 non-structural protein 1 (Nsp1) acts at multiple points toward the host cell to trigger its mRNA cleavage and decay. Nsp1 is found binding with the 40S ribosomal subunit and inhibiting the translation process, as well as docking with different cyclophilins. Herein, we evaluated the structural physicochemical properties of SARS-CoV-2 Nsp1 protein implementing different computational techniques. The Nsp1 was found to form a structured α-helical C-terminal region, following a conformational switch at residue S166 that is necessary for binding the 40S ribosome subunit. Similarly, the presence of cyclophilins stabilizes the Nsp1 C-terminus making a tilt movement at position 166. In the 40S ribosome-Nsp1 machinery, both the ribosomal uS3 and eS30 components were found equally interacting with Nsp1, which guided construction of their pharmacophores. Among a set of studied cyclophilins, FKBP1B showed the highest affinity with Nsp1 and PPIH made least interactions. The majority of cyclophilins dock to the conserved Nsp1 loop or linker region, which connects the C-terminus to the central domain. Our findings revealed that Nsp1 has a versatile C-terminus region which changes its conformations with respect to its host binding partner. Identified novel binding sites within the Nsp1 can assist in understanding its networking (in current or future such infections), as well as support drug discovery programs aimed at targeting the coronavirus family.</p>","PeriodicalId":548,"journal":{"name":"European Biophysics Journal","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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