Journal of structural biology最新文献

{"title":"Nanostructural evolution during carious and demineralisation process of human dentine using small angle X-ray scattering tensor tomography","authors":"Tayyaba Rabnawaz ,&nbsp;Nathanael Leung ,&nbsp;Leonard C. Nielsen ,&nbsp;Robert A. Harper ,&nbsp;Richard M. Shelton ,&nbsp;Gabriel Landini ,&nbsp;Tim Snow ,&nbsp;Andy Smith ,&nbsp;Nick Terrill ,&nbsp;Marianne Liebi ,&nbsp;Tan Sui","doi":"10.1016/j.jsb.2025.108284","DOIUrl":"10.1016/j.jsb.2025.108284","url":null,"abstract":"<div><div>Dental caries, one of the most prevalent non-communicable diseases worldwide, is characterised by the progressive deterioration of the structure and mechanical properties of dental hard tissues. In human teeth, dentine is the most abundant mineralised tissue, forming the primary support material. To assess changes in the mechanical properties of dentine caused by dental caries and acid erosion, it is crucial to understand the relationship between organic and inorganic dentine components and their organisation into a 3D anisotropic structure at the nanoscale. Over the past 20 years, alterations in dentine structure caused by caries and artificial demineralisation have been reported using conventional microscopy techniques. However, due to the limited spatial resolution of these techniques, the 3D structural organisation including orientation and degree of alignment of mineralised collagen fibrils at the nanoscale, has not been fully explored. This study investigated alterations in the 3D structure of normal, carious and artificially demineralised dentine using SAXS tensor tomography (SASTT). This technique enabled the observation of differences in the local orientation of organic and inorganic components, as well as variations in local scattering intensity, resulting from natural caries and artificial demineralisation. In comparison to normal dentine, caries caused minor orientational differences of both components but had a major impact on the local X-ray scattering intensity. After artificial demineralisation of the dentine, most of the mineral was lost in the outer layers, resulting in a greater reduction in scattering intensity than that caused by caries.</div></div><div><h3>Significance</h3><div>The remarkable mechanical properties of human dentine arise from its complex hierarchical 3D structure. In this article, we have investigated the 3D structural alterations in dentine, caused by caries and artificial demineralisation. For this detailed investigation, SAXS tensor tomography (SASTT) has been implemented on the I22 beamline at Diamond Light Source, UK. SASTT is a technique that can probe the nanostructure of dentine, yielding orientation and degree of alignment of the mineralised collagen fibrils, while also providing a 3D reciprocal space map to investigate the detailed non-uniform scattering intensity distribution in all directions. The initial SASTT data provide insights into dentine structural alterations caused by caries and artificial demineralisation, facilitating further exploration of structure–mechanical property relationships, which may lead to improve the development of novel biomimetic materials for dental applications.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"218 1","pages":"Article 108284"},"PeriodicalIF":2.7,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880745","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":"Decoding sequence-structure-function-evolution of basic leucine zippers of aureochromes from heterokont algae","authors":"Madhurima Khamaru,&nbsp;Debarshi Bose,&nbsp;Anwesha Deb,&nbsp;Devrani Mitra","doi":"10.1016/j.jsb.2025.108283","DOIUrl":"10.1016/j.jsb.2025.108283","url":null,"abstract":"<div><div>The blue light photoreceptor cum transcription factors, aureochromes (Aureos), are present exclusively in photosynthetic stramenopiles. Co-existence of Light-Oxygen-Voltage (LOV) and basic leucine zipper (bZIP) is unique to Aureos – therefore ideal to study light-dependent DNA binding/transcriptional regulation. Further, Aureos’ inverse effector-sensor topology, resembling several sensory eukaryotic transcription factors, makes them prototypical optogenetic scaffolds. In absence of 3D data, this study aims for a thorough investigation of the bZIP domains from Aureos and others, and their interaction with substrate DNA using tools from sequence/structural bioinformatics, network theory, molecular dynamics simulation and <em>in vitro</em> experiments. An in-depth comparison of 173 Aureo/plant/opisthokont bZIPs reveals Aureos’ uniqueness and evolutionary significance in DNA binding specificity as well as dimer stability. An all-atom network analysis on representative bZIP-DNA co-crystal structures, especially the measurement of eigenvector centrality, further adds importance to hydrophobic interactions in the zipper region to stabilize bZIP dimer and facilitate DNA binding in Aureos and other bZIPs. The most notable finding is the unique presence of histidine at the basic region of Aureos unlike other bZIPs. Histidine not just promotes blue light independent substrate DNA-binding affinity but also serves as a potential switch point in Aureo/bZIP evolution.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"218 1","pages":"Article 108283"},"PeriodicalIF":2.7,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145862904","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":"Probing the structure and thermodynamics of a multidomain psychrophilic chitinase from Moritella marina","authors":"Magdalena Bejger ,&nbsp;Piotr H. Małecki ,&nbsp;Katarzyna Biniek-Antosiak,&nbsp;Wojciech Rypniewski","doi":"10.1016/j.jsb.2025.108282","DOIUrl":"10.1016/j.jsb.2025.108282","url":null,"abstract":"<div><div>Studies of protein structure and stability have traditionally focused on individual domains, treating them as autonomous units, even though most proteins consist of multiple domains. This raises the question to what extent can multidomain proteins be considered as sums of their individual domains, and how neighboring domains influence one another. Chitinase Chi60 from the psychrophilic bacterium <em>Moritella marina</em> consists of four domains linked in sequence: a catalytic domain, two consecutive Ig-like domains, and a chitin-binding module. The modular architecture of this enzyme provides an opportunity to examine the structure and stability of a protein from which domains are systematically excised. A series of deletion mutants of the chitinase was designed and constructed, and their structures and thermal melting profiles were analyzed. The different domains exhibit distinct melting temperatures. The catalytic domain shows a complex melting profile. Each domain can fold and maintain its structural integrity when isolated, including the two tandem Ig-like domains that share sequence similarity. Although the interfaces between domains in this modular protein are small, it is still possible to detect the influence neighboring domains exert on one another. Some artificial combinations of domains are unstable and prone to degradation. This long, flexible molecule may be stabilized through dimerization when not engaged with the chitin substrate, with two of its domains participating in the interaction.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"218 1","pages":"Article 108282"},"PeriodicalIF":2.7,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850248","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":"Adaptive Gaussian representation for differentiable cryo-electron tomography reconstruction","authors":"Chi Zhang ,&nbsp;Zhidong Yang ,&nbsp;Renmin Han ,&nbsp;Fa Zhang ,&nbsp;Jieqing Feng","doi":"10.1016/j.jsb.2025.108281","DOIUrl":"10.1016/j.jsb.2025.108281","url":null,"abstract":"<div><div>Cryo-electron tomography (cryo-ET) enables 3D visualization of biological structures in their native state, but high-fidelity tomogram reconstruction remains challenging due to low signal-to-noise ratios and limited angular sampling. In this work, we present CryoETGS, a differentiable learning framework that reconstructs tomograms through adaptive 3D Gaussian representations of biological structures for cryo-ET. This representation enables efficient and interpretable reconstruction through a hardware-accelerated differentiable rendering pipeline aligned with the cryo-ET imaging geometry. CryoETGS incorporates hierarchical initialization, adaptive densification, and a tilt-weighted optimization strategy to enhance convergence and reconstruction fidelity. The framework further supports real-time projection synthesis and bidirectional conversion between voxel-based and Gaussian representations. Extensive experiments on both simulated and experimental datasets demonstrate that CryoETGS achieves state-of-the-art reconstruction performance, effectively mitigates missing wedge artifacts, and exhibits high computational efficiency. Source code is publicly available at <span><span>https://github.com/JachyLikeCoding/ETGS</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"218 1","pages":"Article 108281"},"PeriodicalIF":2.7,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794230","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":"Solution 3D structure and conformational flexibility of the endothelial monocyte activating polypeptide II (EMAP II) revealed by NMR spectroscopy and molecular dynamics simulations","authors":"Dmytro Lozhko ,&nbsp;Lesia Kolomiiets ,&nbsp;Lilia Zhukova ,&nbsp;Michal Taube ,&nbsp;Maciej Kozak ,&nbsp;Michał Dadlez ,&nbsp;Olexandr Kornelyuk ,&nbsp;Igor Zhukov","doi":"10.1016/j.jsb.2025.108280","DOIUrl":"10.1016/j.jsb.2025.108280","url":null,"abstract":"<div><div>Endothelial monocyte activating polypeptide II (EMAP II) is the C-terminal domain of its precursor, AIMP1/p43 polypeptide, a multifunctional protein with diverse functional cytokine activities and tRNA-binding abilities. Several X-ray crystallographic structures of EMAP II are available in the PDB database. However, its NMR-based structure, presented in this work indicates partition of its structure into two domains characterized by substantial differences in structural dynamics. Based on ¹⁵N relaxation experiments, hydrogen–deuterium exchange (HDX) data and molecular dynamics simulations we conclude that observed differences in dynamics may enable dual mechanisms of tRNA binding and cytokine function of EMAP II. Although in general in-solution EMAP II structure studied here is highly similar to its in-crystal X-ray structure, the N-terminal segment responsible for cytokine activity exhibited reduced deuterium exchange rate and demonstrated higher accessibility to the solvent compared to X-ray structures and the <em>AlphaFold2</em> model. Such differences may be important for understanding cytokine function of EMAP II. The tRNA-binding motif characterized by different orientation of the side chain of tryptophan 128, which can play a significant role in the regulation of tRNA binding.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"218 1","pages":"Article 108280"},"PeriodicalIF":2.7,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145763008","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":"From selenium to sulfur: predictive modeling unveils conformational and bonding changes in selenoproteins","authors":"Shiqi Luo ,&nbsp;Xinnan Liu ,&nbsp;Xia Wang ,&nbsp;Haotian Liu ,&nbsp;Wei Ge","doi":"10.1016/j.jsb.2025.108278","DOIUrl":"10.1016/j.jsb.2025.108278","url":null,"abstract":"<div><div>Selenoproteins, defined by the incorporation of the 21st amino acid — selenocysteine (Sec) — orchestrate essential redox, endocrine, and metabolic pathways in humans, yet high‑resolution structures exist for only a minority of the 25 family members. Leveraging the AlphaFold 3 (AF3), we generated full‑length atomic models for all human selenoproteins together with in‑silico Sec-to-Cys variants. AF3 achieved high confidence for 22 proteins and sub‑Å agreement with the one experimentally solved glutathione peroxidase 4 (GPX4). Global comparison of native and mutant models revealed that Sec-to-Cys substitution preserves overall fold in nineteen proteins but locally disrupts or re‑wires intramolecular selenenyl‑sulfide linkages in six cases. Structure‑based clustering uncovered a conserved “Se‑thioredoxin‑like” core in fifteen selenoproteins. AF3 additionally predicted potential GPX4 homodimeric assemblies, consistent with the dimeric forms observed in native gels from brain tissue and cell lines. Together, these AF3 models constitute the comprehensive structural atlas of the human selenoproteome, elucidate the fold‑specific positioning of Sec. The dataset provides a foundation for mechanistic dissection, evolutionary analyses, and rational drug design targeting selenium‑dependent redox biology.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"218 1","pages":"Article 108278"},"PeriodicalIF":2.7,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743108","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":"Announcement: Journal of Structural Biology: Paper of the year.","authors":"Sergio Pantano","doi":"10.1016/j.jsb.2025.108275","DOIUrl":"10.1016/j.jsb.2025.108275","url":null,"abstract":"","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":" ","pages":"108275"},"PeriodicalIF":2.7,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743145","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":"Mechanistic study of PDE5A inhibitors from the prepared folium of Epimedium sagittatum maxim","authors":"Yuan Fang ,&nbsp;Siqi Wu ,&nbsp;Jian Xu ,&nbsp;Jialiang Chen ,&nbsp;Wanyin Shi ,&nbsp;Hongji Wang ,&nbsp;Senjie Li ,&nbsp;Huifang Xie ,&nbsp;Houchao Tao ,&nbsp;Lifeng Pan ,&nbsp;Yunxiang Zang ,&nbsp;Guangtao Yao ,&nbsp;Xiangwei Zheng","doi":"10.1016/j.jsb.2025.108279","DOIUrl":"10.1016/j.jsb.2025.108279","url":null,"abstract":"<div><div>Phosphodiesterase-5 (PDE5A) is a critical therapeutic target for treating male erectile dysfunction (ED). PDE5A inhibitors like sildenafil are clinically effective, but exhibit side effects due to non-specific inhibition of related PDE isoforms. This necessitates the discovery of safer and specific PDE5A inhibitors. The prepared folium of Epimedium sagittatum (PFES) is a primary sovereign drug in traditional Chinese medicine (TCM) formulations for ED. As part of ongoing research into its pharmacodynamic basis, this study isolated and identified forty-four flavonoids and organic acids from PFES. The inhibitory activities of these compounds against PDE5A were systematically evaluated, and three compounds (1, 5, and 6) are demonstrated to have significant PDE5A inhibition activities. Notably, the compound 6 (baohuoside I), was previously confirmed the activity<!--> <!-->with PDE5A, and its co-crystal structure with PDE5A was also reported. To elucidate the molecular mechanisms underlying the inhibition of PDE5A by compound 1 and 5, we solved the crystal structures of the catalytic domain of PDE5A in complex with compound 1 and 5. Further structural analyses revealed distinct binding modes adopted by 1 and 5 for occupying the PDE5A active site, highlighting their specific interactions with PDE5A compared to each other and to other established inhibitors like sildenafil. In summary, these findings underscore the potential of PFES-derived natural compounds as specific PDE5A inhibitors, and provide crucial insights for the rational development of novel ED therapeutics with potentially improved specificity and reduced side effects based on TCM constituents.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"218 1","pages":"Article 108279"},"PeriodicalIF":2.7,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743137","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":"Structural characterization of Meiothermus ruber LOV domain","authors":"Oleg Semenov ,&nbsp;Vera Nazarenko ,&nbsp;Anna Yudenko ,&nbsp;Kirill Kovalev ,&nbsp;Ivan Goncharov ,&nbsp;Ilia Natarov ,&nbsp;Anatolii Mikhailov ,&nbsp;Elizaveta Kuznetsova ,&nbsp;Andrey Nikolaev ,&nbsp;Yuqi Yang ,&nbsp;Nikolai N. Sluchanko ,&nbsp;Valentin Borshchevskiy ,&nbsp;Alina Remeeva ,&nbsp;Ivan Gushchin","doi":"10.1016/j.jsb.2025.108268","DOIUrl":"10.1016/j.jsb.2025.108268","url":null,"abstract":"<div><div>Light Oxygen Voltage (LOV) domains are important widespread receptors of blue light that also found applications in optogenetics and imaging. While LOV domains from mesophiles are relatively well characterized, their counterparts from thermophilic microorganisms remain understudied. Here, we express two constructs of a LOV domain belonging to a histidine kinase from <em>Meiothermus ruber</em>, MrLOV and MrLOVe, and show that they are photoactive, with recovery time values of 21 and 27 min, respectively, and thermostable. Crystal structures reveal that MrLOV, which lacks helices A’α and Jα, forms a parallel dimer, whereas MrLOVe is a tetramer organized as an antiparallel dimer of two parallel dimers interacting via helices Jα. One MrLOVe dimer is symmetric, and the other is asymmetric, with conformational differences mirroring activation-related changes in other LOV domains. Our data provide the structural basis for understanding and engineering of thermophilic LOVs and pave the way for development of thermostable and photostable LOV-derived optogenetic tools and flavin-based fluorescent proteins.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"218 1","pages":"Article 108268"},"PeriodicalIF":2.7,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687600","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":"Announcement: Journal of Structural Biology: Paper of the year","authors":"Moon Ki Kim","doi":"10.1016/j.jsb.2025.108263","DOIUrl":"10.1016/j.jsb.2025.108263","url":null,"abstract":"","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 4","pages":"Article 108263"},"PeriodicalIF":2.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145635008","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}