Journal of structural biology最新文献

{"title":"Structural organization of the organic sheath that delineates extracellular seta silicification in diatoms","authors":"Razi Safadi,&nbsp;Lior Aram,&nbsp;Diede de Haan,&nbsp;Emanuel M. Avrahami,&nbsp;Assaf Gal","doi":"10.1016/j.jsb.2025.108205","DOIUrl":"10.1016/j.jsb.2025.108205","url":null,"abstract":"<div><div>Nanopatterning of inorganic materials is a challenging task for contemporary science. It is therefore remarkable that unicellular organisms can form intricately shaped biominerals. A prominent example is the silica cell wall of diatoms, which usually forms in specialized intracellular organelles. Inside such an organelle, biological regulation proceeds via the concerted activity of various organic macromolecules and inorganic precursors. However, it was shown that a specific type of elongated silica structures, called setae, which characterizes the diatom genus <em>Chaetoceros</em>, form extracellularly, raising questions about the regulatory mechanisms of this silicification process. Here, we study a relatively large species, <em>Chaetoceros rostratus</em>, that forms long and intricate setae. We used in-cell cryo electron tomography to image the native state of seta formation. The high-resolution 3D data show that silica formation outside the cell membrane involves continuous organic sheath that covers the newly formed seta. This sheath has an elaborate structure and is positioned tens of nanometers away from the silica by structural macromolecules that might be involved in architectural regulation. Elucidating the structural components of this delicate living system will allow for new opportunities to learn about the biological strategies for controlled mineralization.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108205"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Gα C-terminal deletion on the intrinsic GDP release/GTPase activity and conformational dynamics","authors":"Junyoung Kim,&nbsp;Ka Young Chung","doi":"10.1016/j.jsb.2025.108182","DOIUrl":"10.1016/j.jsb.2025.108182","url":null,"abstract":"<div><div>Heterotrimeric G proteins (G proteins) serve as key signaling mediators downstream of G protein-coupled receptors (GPCRs). Comprised of Gα, Gβ, and Gγ subunits, the activation state of Gα, determined by GDP or GTP binding, governs G protein activity. While high-resolution structures of GPCR-G protein complexes have identified the Gα C-terminal 5 residues (<em>i.e.,</em> wavy hook) as critical for GPCR binding and coupling selectivity, its influence on Gα’s intrinsic biochemical properties remains unclear. Here, we investigated the role of wavy hook truncation in the intrinsic GDP/GTP turnover rate, GTPase activity, and conformational dynamics of Gαs and Gαi1 using BODIPY-labeled nucleotides and hydrogen/deuterium exchange mass spectrometry (HDX-MS). Truncation of the wavy hook significantly altered the GDP/GTP turnover rate, GTPase activity, and conformational flexibility of Gαs, particularly at the p-loop through α1 region, but had minimal impact on Gαi1. These findings reveal subtype-specific effects of the wavy hook on G protein stability and conformational dynamics, highlighting the importance of structural elements in regulating G protein function and their implications for GPCR signaling studies.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108182"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcium carbonate deposition in the spicules of the sponge Heteropia glomerosa (Porifera, Calcarea)","authors":"Camila Wendt ,&nbsp;Fernanda C. de Medeiros ,&nbsp;Raquel P. Gonçalves ,&nbsp;Fabio Nudelman ,&nbsp;Michelle Klautau ,&nbsp;Marcos Farina ,&nbsp;André L. Rossi","doi":"10.1016/j.jsb.2025.108210","DOIUrl":"10.1016/j.jsb.2025.108210","url":null,"abstract":"<div><div>We investigated the biomineralization process of calcium carbonate deposition in the spicules of the calcareous sponge <em>Heteropia glomerosa</em> (Porifera, Calcarea). The finely polished spicules, composed of Mg-calcite, present a pattern of concentric lines spaced 400 nm apart when observed by scanning electron microscopy. We showed by electron backscattered diffraction that the whole spicule length has the same crystallographic orientation. Still, misorientation of up to 1.8° in adjacent regions (∼ 2 µm) and a continuous increase in the misalignment of up to 4.5° in regions separated by 300 µm were present. The sponge cells (mainly sclerocytes and pinacocytes) near the mineralization zone contain a high number of vesicles rich in calcium, which could be involved in the spicule biomineralization. We showed by electron and ion microscopies that the spicule growth occurs through the addition calcium carbonate granules, which form near the membrane of the sclerocyte, the cell responsible for biomineralization. The granules were deposited layer by layer on the surface of the spicule, increasing the biomineral thickness. Domains of 1–3 µm containing facets partially connected and surrounded by organic material were observed in an intermediate stage of the spicule growth. Misorientation between these domains was approximately 2°, similar to the misorientation obtained by electron backscattered diffraction, indicating that the spicule is formed by the addition of granules fusing in a predominant orientation.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108210"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2.0 Å cryo-EM structure of the 55 kDa nucleoplasmin domain of AtFKBP53","authors":"Nikhil Bharambe ,&nbsp;Ketul Saharan ,&nbsp;Dileep Vasudevan ,&nbsp;Sandip Basak","doi":"10.1016/j.jsb.2025.108203","DOIUrl":"10.1016/j.jsb.2025.108203","url":null,"abstract":"<div><div>The knowledge of three-dimensional structures of biological macromolecules is crucial for understanding the molecular mechanisms underlying disease pathology and for devising drugs targeting specific molecules. Single particle cryo-electron microscopy (Cryo-EM) has become indispensable for this purpose, particularly for large macromolecules and their complexes. However, its effectiveness has been limited in achieving near-atomic resolution for smaller macromolecules. This study presents the Cryo-EM structure of a 55 kDa pentameric AtFKBP53 nucleoplasmin domain at 2.0 Å nominal resolution. Our approach involves selecting the optimal grid for data collection and precise alignment of small particles to enhance the resolution of the final 3D reconstructed map. In this study, we systematically processed cryo-EM dataset of a small molecule to improve alignment, and this data processing strategy can be used as a guidance to process the cryo-EM data of other small molecules.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108203"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determinants of site-selectivity in human ileal bile acid-binding protein by NMR dynamic analysis of a functionally-impaired mutant","authors":"Tamara Teski ,&nbsp;Gergő Horváth ,&nbsp;Orsolya Toke","doi":"10.1016/j.jsb.2025.108202","DOIUrl":"10.1016/j.jsb.2025.108202","url":null,"abstract":"<div><div>Human ileal bile acid-binding protein (hI-BABP), a member of the family of intracellular lipid-binding proteins, has a key role in the enterohepatic circulation of bile salts. The two internal binding sites of hI-BABP exhibit positive cooperativity accompanied by a site preference of glycocholate (GCA) and glycochenodeoxycholate (GCDA), the two most abundant bile salts in the human body. Previous study of Q51A hI-BABP in its <em>apo</em> state, a mutant with lost site-selectivity, suggests that disruption of the hydrogen-bonding network in the vicinity of the C/D-turn has long-range dynamic effects. To improve our understanding of the determinants of site-selectivity in hI-BABP, a comparative NMR chemical shift and spin relaxation analysis of homo- and heterotypic bile salt complexes of wild-type and Q51A hI-BABP was carried out. The wild-type GCDA-complex shows a striking similarity with the thermodynamically most stable hI-BABP:GCDA:GCA complex in terms of both structure and dynamic behaviour, suggesting that the bound GCDA at site 1 has a decisive role in conveying key stabilizing interactions in the physiologically most abundant heterotypic complex. Destabilization of hI-BABP-GCDA by the functionally impairing mutation Q51A is indicated by both the increase of ms-timescale motions in key segments of the protein as well as by increased ps-ns local fluctuations superimposed on slow motions. Our study suggests that binding interactions in hI-BABP might be modulated by altering the dynamic behaviour of specific segments in the protein with implications for targeting the intracellular trafficking of bile salts and bile salt-induced stimulation of nuclear receptors.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108202"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of conformational flexibility in protein structures by applying artificial intelligence to molecular modeling","authors":"Kirill Kopylov ,&nbsp;Evgeny Kirilin ,&nbsp;Vladimir Voevodin ,&nbsp;Vytas Švedas","doi":"10.1016/j.jsb.2025.108204","DOIUrl":"10.1016/j.jsb.2025.108204","url":null,"abstract":"<div><div>Recent AI applications have revolutionized the modeling of structurally unresolved protein regions, thereby complementing traditional computational methods. These state-of-the-art techniques can generate numerous candidate structures, significantly expanding the scope of structural biology. However, to effectively prioritize these models, a physics-based approach is required to assess the energy landscape. Such integration can bridge the gap between rapid model generation and precise determination of functional conformations. To address this challenge, we propose an integrated approach that combines molecular modeling with AI and HPC. Metadynamics simulations in latent space are used to explore potential energy landscapes based on initial approximations of flexible region structures derived from modeling tools such as AlphaFold, RosettaFold, Modeller, SwissModel, etc. The approach was validated by modeling folding of Trp-cage protein and conformational plasticity of ubiquitin. The predominant conformations of previously unresolved mobile regions in the active center of flavin-dependent 2-hydroxybiphenyl-3-monooxygenase (EC 1.14.13.44) were identified, while estimating the energy associated with these conformational changes.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108204"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mechanism underlying fascin-mediated bundling of actin filaments unveiled by cryo-electron tomography","authors":"Xiyong Song ,&nbsp;Jesús Baltanás-Copado ,&nbsp;Muniyandi Selvaraj ,&nbsp;Shrikant B. Kokate ,&nbsp;Esa-Pekka Kumpula ,&nbsp;Senena Corbalán-García ,&nbsp;Juha T. Huiskonen","doi":"10.1016/j.jsb.2025.108212","DOIUrl":"10.1016/j.jsb.2025.108212","url":null,"abstract":"<div><div>Fascins are crucial actin-binding proteins linked to carcinomas, such as cancer metastasis. Fascins crosslink unipolar actin filaments into linear and rigid parallel bundles, which play essential roles in the formation of filopodia, stereocilia and other membrane protrusions. However, the mechanism of how fascin bundles actin filaments has remained elusive. Here, we studied the organization of reconstituted fascin-actin bundles by cryo-electron tomography and determined the structure of the fascin–actin complex at 9 Å resolution by subtomogram averaging. Consistent with earlier findings, fascin molecules decorate adjacent actin filaments, positioned at regular intervals corresponding to the half-pitch of actin filaments. The fascin–actin complex structure allows us to verify the binding orientation of fascin between the two actin filaments. Fitting of the previously solved fascin crystal structure facilitates the analysis of the interaction surfaces. Our structural models serve as a blueprint to understand the detailed interactions between fascin and actins and provide new insights for the development of drugs targeting fascin proteins.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108212"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phylogenetic analysis and structural studies of heteromeric acetyl-CoA carboxylase from the oleaginous Amazonian microalgae Ankistrodesmus sp.: Insights into the BC and BCCP subunits","authors":"Andry Mercedes Mavila ,&nbsp;Jhon Antoni Vargas ,&nbsp;Eloy Condori ,&nbsp;Erick Giancarlo Suclupe Farro ,&nbsp;Adriano Alves Furtado ,&nbsp;Josué Manuel López ,&nbsp;Silvia Lucila Gonzalez ,&nbsp;Humberto D’Muniz Pereira ,&nbsp;Jorge Luis Marapara ,&nbsp;Roger Ruiz Paredes ,&nbsp;Marianela Cobos ,&nbsp;Juan C. Castro ,&nbsp;Richard Charles Garratt ,&nbsp;Diego Antonio Leonardo","doi":"10.1016/j.jsb.2025.108200","DOIUrl":"10.1016/j.jsb.2025.108200","url":null,"abstract":"<div><div>Acetyl-CoA carboxylase (ACC) is an essential enzyme in fatty acid biosynthesis that catalyzes the formation of malonyl-CoA from acetyl-CoA. While structural studies on ACC components have largely focused on prokaryotes and higher plants, the assembly and molecular adaptations of ACC in microalgae remain underexplored. This study aimed to fill this gap by providing the first structural and evolutionary characterization of both biotin carboxylase (BC) and biotin carboxyl carrier protein (BCCP) from a microalga (<em>Ankistrodesmus</em> sp.<em>)</em>. Phylogenetic analysis revealed distinct evolutionary trajectories for BC and BCCP, with BC forming a chlorophyte-specific clade closely related to other oleaginous species, while BCCP displayed two distinct isoforms within green algae, resulting from gene duplication. The crystallographic structure of BC was solved in its apo (1.75 Å) and ADP-Mg²⁺-bound (1.90 Å) states, revealing conserved conformational changes associated with cofactor binding. BCCP from <em>Ankistrodesmus</em> sp. displayed a unique QLGTF/H motif instead of the canonical AMKXM biotinylation motif, suggesting loss of biotinylation capacity. However, the presence of three additional lysines in the protruding thumb loop, with Lys95 as a candidate for biotin attachment, indicates potential compensatory adaptations. SEC-MALS and pull-down assays confirmed the formation of a stable 1:1 BC-BCCP complex, and circular dichroism showed increased thermal stability of the complex, supporting its structural stability. This study highlights unique structural adaptations in <em>Ankistrodesmus</em> sp. ACC, emphasizing the evolutionary plasticity of BC and BCCP. These insights provide a foundation for future investigations into ACC regulation in photosynthetic organisms and offer potential biotechnological applications for optimizing lipid production in microalgae.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108200"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMR and semi-synthesis in synergy to study protein regulation","authors":"Thibault Viennet","doi":"10.1016/j.jsb.2025.108192","DOIUrl":"10.1016/j.jsb.2025.108192","url":null,"abstract":"<div><div>Structural biology as a field has advanced immensely in the last few years, but the mechanistic roles of protein disordered regions and their associated post-translational modifications on the molecular level are still poorly understood. Nuclear magnetic resonance offers the possibility to investigate these regions with atomic resolution and understand the effect of protein modification, and thus protein regulation. However, obtaining suitable and well-defined samples is not straightforward. Here, I review some approaches to protein semi-synthesis for nuclear magnetic resonance purposes, and their applications. I hope to demonstrate that these chemical and structural biology techniques create a powerful synergy that enables structural studies of protein regulation.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108192"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dengue virus-host interactions: Structural and mechanistic insights for future therapeutic strategies","authors":"Moumita Khanra ,&nbsp;Indrani Ghosh ,&nbsp;Samima Khatun ,&nbsp;Nilanjan Ghosh ,&nbsp;Shovanlal Gayen","doi":"10.1016/j.jsb.2025.108196","DOIUrl":"10.1016/j.jsb.2025.108196","url":null,"abstract":"<div><div>Dengue pathogen, transmitted by mosquitoes, poses a growing threat as it is capable of inflicting severe illness in humans. Around 40% of the global population is currently affected by the virus, resulting in thousands of fatalities each year. The genetic blueprint of the virus comprises 10 proteins. Three proteins serve as structural components: the capsid (C), the precursor of the membrane protein (PrM/M), and the envelope protein (E). The other proteins serve as non-structural (NS) proteins, consisting of NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5. The virus relies on these NS proteins to expropriate host proteins for its replication. During their intracellular replication, these viruses engage with numerous host components and exploit the cellular machinery for tasks such as entry into various organs, propagation, and transmission. This review explores mainly the relationship between dengue viral protein and host proteins elucidating the development of viral-host interactions. These relationships between the virus and the host give important information on the processes behind viral replication and the etiology of disease, which in turn facilitates the creation of more potent treatment strategies.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108196"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}