Journal of structural biology最新文献_第9页

Dengue virus-host interactions: Structural and mechanistic insights for future therapeutic strategies 登革病毒-宿主相互作用：未来治疗策略的结构和机制见解。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-06-01 Epub Date: 2025-03-14 DOI: 10.1016/j.jsb.2025.108196

Moumita Khanra , Indrani Ghosh , Samima Khatun , Nilanjan Ghosh , Shovanlal Gayen

{"title":"Dengue virus-host interactions: Structural and mechanistic insights for future therapeutic strategies","authors":"Moumita Khanra , Indrani Ghosh , Samima Khatun , Nilanjan Ghosh , 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}

引用次数: 0

3D Multi-modal Imaging of demineralised dentine using combined synchrotron µ-XRD-CT and STXM-CT 同步加速器μ-XRD-CT与STXM-CT联合三维多模态成像牙本质脱矿。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-06-01 Epub Date: 2025-05-16 DOI: 10.1016/j.jsb.2025.108208

Nathanael Leung , Robert A. Harper , Bin Zhu , Stuart A. Bartlett , Konstantin Ignatyev , Richard M. Shelton , Gabriel Landini , Tan Sui

{"title":"3D Multi-modal Imaging of demineralised dentine using combined synchrotron µ-XRD-CT and STXM-CT","authors":"Nathanael Leung , Robert A. Harper , Bin Zhu , Stuart A. Bartlett , Konstantin Ignatyev , Richard M. Shelton , Gabriel Landini , Tan Sui","doi":"10.1016/j.jsb.2025.108208","DOIUrl":"10.1016/j.jsb.2025.108208","url":null,"abstract":"<div><div>Dental caries is the most prevalent oral disease that causes structural and compositional changes of the dental hard tissues due to a chronic demineralisation (combined with possible phases of remineralisation) process. Though considerable efforts have been directed at studying natural and artificial carious lesions, most characterisations remain either constrained to 2D analyses or have been unable to achieve fine resolution in 3D due to limited field of view. To overcome this challenge, the present study combined X-ray diffraction (XRD) and scanning transmission X-ray microscopy (STXM) tomography techniques to analyse the mineral density, scattering intensity, and crystallite size in normal, carious, 30 % artificially demineralised, and 50 % artificially demineralised dentine. Combined XRD and STXM tomography was performed on the I18 beamline at Diamond Light Source, using a 15 keV monochromatic beam with 2 × 2 µm spotsize and scanning with translation steps of 2 µm, providing a reconstructed voxel size of 2 × 2 × 2 µm. Natural carious dentine showed a reduction in hydroxyapatite (HAp) crystallite size due to chronic demineralisation. This was unlike artificially demineralised dentine samples that underwent short, continuous demineralisation, which created a zone of fully demineralised dentine, near the sample surface, and a zone of partially demineralised dentine that had a reduced mineral density but an increased average crystallite size.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108208"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094151","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}

引用次数: 0

Conformational landscape of the mycobacterial inosine 5′-monophosphate dehydrogenase octamerization interface 分枝杆菌肌苷5'-单磷酸脱氢酶八聚界面的构象景观。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-06-01 Epub Date: 2025-03-17 DOI: 10.1016/j.jsb.2025.108198

Ondřej Bulvas, Zdeněk Knejzlík, Anatolij Filimoněnko, Tomáš Kouba, Iva Pichová

{"title":"Conformational landscape of the mycobacterial inosine 5′-monophosphate dehydrogenase octamerization interface","authors":"Ondřej Bulvas, Zdeněk Knejzlík, Anatolij Filimoněnko, Tomáš Kouba, Iva Pichová","doi":"10.1016/j.jsb.2025.108198","DOIUrl":"10.1016/j.jsb.2025.108198","url":null,"abstract":"<div><div>Inosine 5′-monophosphate dehydrogenase (IMPDH), a key enzyme in bacterial purine metabolism, plays an essential role in the biosynthesis of guanine nucleotides and shows promise as a target for antimicrobial drug development. Despite its significance, the conformational dynamics and substrate-induced structural changes in bacterial IMPDH remain poorly understood, particularly with respect to its octameric assembly. Using cryo-EM, we present full-length structures of IMPDH from <em>Mycobacterium smegmatis</em> (<em>Msm</em>IMPDH) captured in a reaction intermediate state, revealing conformational changes upon substrate binding. The structures feature resolved flexible loops that coordinate the binding of the substrate, the cofactor, and the K<sup>+</sup> ion. Our structural analysis identifies a novel octamerization interface unique to <em>Msm</em>IMPDH. Additionally, a previously unobserved barrel-like density suggests potential self-interactions within the C-terminal regions, hinting at a regulatory mechanism tied to assembly and function of the enzyme. These data provide insights into substrate-induced conformational dynamics and novel interaction interfaces in <em>Msm</em>IMPDH, potentially informing the development of IMPDH-targeted drugs.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108198"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663821","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}

引用次数: 0

AITom: AI-guided cryo-electron tomography image analyses toolkit ai引导的低温电子断层成像图像分析工具包

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-06-01 Epub Date: 2025-05-14 DOI: 10.1016/j.jsb.2025.108207

Xueying Zhan , Xiangrui Zeng , Mostofa Rafid Uddin, Min Xu

{"title":"AITom: AI-guided cryo-electron tomography image analyses toolkit","authors":"Xueying Zhan , Xiangrui Zeng , Mostofa Rafid Uddin, Min Xu","doi":"10.1016/j.jsb.2025.108207","DOIUrl":"10.1016/j.jsb.2025.108207","url":null,"abstract":"<div><div>Cryo-electron tomography (cryo-ET) is an essential tool in structural biology, uniquely capable of visualizing three-dimensional macromolecular complexes within their native cellular environments, thereby providing profound molecular-level insights. Despite its significant promise, cryo-ET faces persistent challenges in the systematic localization, identification, segmentation, and structural recovery of three-dimensional subcellular components, necessitating the development of efficient and accurate large-scale image analysis methods. In response to these complexities, this paper introduces <span>AITom</span>, an open-source artificial intelligence platform tailored for cryo-ET researchers. <span>AITom</span> integrates a comprehensive suite of public and proprietary algorithms, supporting both traditional template-based and template-free approaches, alongside state-of-the-art deep learning methodologies for cryo-ET data analysis. By incorporating diverse computational strategies, <span>AITom</span> enables researchers to more effectively tackle the complexities inherent in cryo-ET, facilitating precise analysis and interpretation of complex biological structures. Furthermore, <span>AITom</span> provides extensive tutorials for each analysis module, offering valuable guidance to users in utilizing its comprehensive functionalities.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108207"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068286","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}

引用次数: 0

Computational identification of B and T-cell epitopes for designing a multi-epitope vaccine against SARS-CoV-2 spike glycoprotein 设计抗SARS-CoV-2刺突糖蛋白多表位疫苗的B细胞和t细胞表位的计算鉴定

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-06-01 Epub Date: 2025-02-11 DOI: 10.1016/j.jsb.2025.108177

Truc Ly Nguyen , Thong Ba Nguyen , Heebal Kim

{"title":"Computational identification of B and T-cell epitopes for designing a multi-epitope vaccine against SARS-CoV-2 spike glycoprotein","authors":"Truc Ly Nguyen , Thong Ba Nguyen , Heebal Kim","doi":"10.1016/j.jsb.2025.108177","DOIUrl":"10.1016/j.jsb.2025.108177","url":null,"abstract":"<div><div>Although the peak of the COVID-19 pandemic has passed, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose a significant global threat and remains a public health concern. Given the ongoing risk and the substantial loss of life caused by the virus, continuous research into vaccine development is essential. This study employs immunoinformatics approaches to identify T-cell and B-cell epitopes for designing a multi-epitope peptide vaccine candidate targeting the Omicron variant. The proposed vaccine construct comprises 1435 amino acids, including eight linear B lymphocyte, seven cytotoxic T lymphocyte, and five helper T lymphocyte epitopes, along with appropriate adjuvants and linkers. The evaluation of the vaccine revealed high antigenicity, non-allergenicity, non-toxicity, and favorable physicochemical properties. To further assess its efficacy, molecular docking studies were performed to investigate interactions between the vaccine and key immune components, including Toll-like receptors and major histocompatibility complex molecules. Stability of these interactions was confirmed using molecular dynamics simulations in triplicate, conducted over 100 ns using GROMACS 2023 to compute key metrics, such as root mean square deviation, root mean square fluctuation, solvent-accessible surface area, and radius of gyration. The results demonstrate that the multi-epitope vaccine has the potential to elicit strong immune responses against the Omicron variant, providing a promising foundation for further experimental validation and clinical development in COVID-19 vaccine research.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108177"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414501","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}

引用次数: 0

Untangling the effects of flexibility and the AWI in cryoEM sample preparation: A case study using KtrA 解开低温样品制备中灵活性和AWI的影响：使用KtrA的案例研究

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-06-01 Epub Date: 2025-05-03 DOI: 10.1016/j.jsb.2025.108206

Isobel Jackson Hirst , Wesley Tien Chiang , Nien-Jen Hu , Charlotte A. Scarff , Rebecca F. Thompson , Michele C. Darrow , Stephen P. Muench

{"title":"Untangling the effects of flexibility and the AWI in cryoEM sample preparation: A case study using KtrA","authors":"Isobel Jackson Hirst , Wesley Tien Chiang , Nien-Jen Hu , Charlotte A. Scarff , Rebecca F. Thompson , Michele C. Darrow , Stephen P. Muench","doi":"10.1016/j.jsb.2025.108206","DOIUrl":"10.1016/j.jsb.2025.108206","url":null,"abstract":"<div><div>Single particle cryo-electron microscopy (cryoEM) is a powerful tool for elucidating the structures of biological macromolecules without requiring crystallisation or fixation. However, certain barriers to obtaining high-resolution structures persist, particularly during grid preparation when samples are in a thin liquid film. At this stage, extensive exposure to the air–water interface (AWI) can lead to subunit dissociation, denaturation, and preferred orientation of particles. Another obstacle to high-resolution cryoEM is molecular flexibility, which introduces heterogeneity in the dataset, weakening the signal during image processing. This study explores the effects of AWI interactions and molecular flexibility on the cryoEM density maps of KtrA, the soluble regulatory subunit of the potassium transporter KtrAB from <em>Bacillus subtilis</em>. From grids prepared using a standard blotting technique, we observed a lack of density in the C-lobe domains and preferred orientation. Modifications such as reducing AWI exposure through faster vitrification times (6 s vs ≤100 ms) notably improved C-lobe density. Moreover, the addition of cyclic di-AMP, which binds to the C-lobes, combined with a 100 ms plunge time, further enhanced C-lobe density and eliminated preferred orientation. These findings demonstrate that both AWI interactions and flexibility had to be addressed to obtain density for the C-lobe domains of KtrA. This study underscores the ongoing complexities in achieving high-resolution cryoEM for many samples.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108206"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941077","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}

引用次数: 0

A non-parametric approach to particle picking in all frames 在所有帧中进行粒子拾取的非参数方法。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-06-01 Epub Date: 2025-05-05 DOI: 10.1016/j.jsb.2025.108201

Evgeny Hershkovitch Neiterman , Ayelet Heimowitz , Gil Ben-Artzi

引用次数: 0

Mechanistic insights into cyclodextrins as substrates and inhibitors of GH57 family amylopullulanase from Aquifex aeolicus 环糊精作为水蛭GH57家族淀粉葡聚糖酶底物和抑制剂的机制研究。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-06-01 Epub Date: 2025-03-20 DOI: 10.1016/j.jsb.2025.108199

Zhimin Zhu , Minjun Li , Qin Xu , Liqing Huang , Huan Zhou , Weiwei Wang , Qisheng Wang , Feng Yu

{"title":"Mechanistic insights into cyclodextrins as substrates and inhibitors of GH57 family amylopullulanase from Aquifex aeolicus","authors":"Zhimin Zhu , Minjun Li , Qin Xu , Liqing Huang , Huan Zhou , Weiwei Wang , Qisheng Wang , Feng Yu","doi":"10.1016/j.jsb.2025.108199","DOIUrl":"10.1016/j.jsb.2025.108199","url":null,"abstract":"<div><div>Maltooligosaccharides (MOs) have gained significant attention in the food and pharmaceutical industries owing to their valuable functional properties, including controlled sweetness, digestibility, and enhanced bioavailability. However, conventional MOs is production involves complex processing steps and significant production costs. A potential high-efficiency synthesis of specific MOs can be achieved through the ring-opening reaction of cyclodextrins (CDs) catalyzed by amylolytic enzymes. In this study, we analyze the catalytic conversion of α-, β-, and γ-CDs by a GH57 family amylopullulanase from <em>Aquifex aeolicus</em> (AaApu) using thin-layer chromatography (TLC). Our findings demonstrate that AaApu has a substrate specificity for γ-CD, while all three CDs exert competitive inhibition on pullulan hydrolysis. To elucidate the molecular mechanism of CDs as inhibitor and substrate of amylopullulanase, we determined high-resolution crystal structures of AaApu (wild-type and D352N) in complex with α-, β-, and γ-CD through co-crystallization. These findings establish a structure–function framework for understanding the bifunctional nature of CDs as both substrates and inhibitors in GH57 amylopullulanases.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108199"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692443","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}

引用次数: 0

RosettaHDX: Predicting antibody-antigen interaction from hydrogen-deuterium exchange mass spectrometry data RosettaHDX：从氢-氘交换质谱数据预测抗体-抗原相互作用。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-03-01 Epub Date: 2025-01-05 DOI: 10.1016/j.jsb.2025.108166

Minh H. Tran , Cristina E. Martina , Rocco Moretti , Marcus Nagel , Kevin L. Schey , Jens Meiler

{"title":"RosettaHDX: Predicting antibody-antigen interaction from hydrogen-deuterium exchange mass spectrometry data","authors":"Minh H. Tran , Cristina E. Martina , Rocco Moretti , Marcus Nagel , Kevin L. Schey , Jens Meiler","doi":"10.1016/j.jsb.2025.108166","DOIUrl":"10.1016/j.jsb.2025.108166","url":null,"abstract":"<div><div>High-throughput characterization of antibody-antigen complexes at the atomic level is critical for understanding antibody function and enabling therapeutic development. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) enables rapid epitope mapping, but its data are too sparse for independent structure determination. In this study, we introduce RosettaHDX, a hybrid method that combines computational docking with differential HDX-MS data to enhance the accuracy of antibody-antigen complex models beyond what either method can achieve individually. By incorporating HDX data as both distance restraints and a scoring term in the RosettaDock algorithm, RosettaHDX successfully generated near-native models (interface root-mean square deviation ≤ 4 Å) for all 9 benchmark complexes examined, averaging 3.6 times more near-native models than Rosetta alone. Near-native models among the top 10 scoring were identified in 3/9 cases, compared to 1/9 with Rosetta alone. Additionally, we developed a predictive metric based on docking results with HDX restraints to identify allosteric peptides in HDX datasets.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 1","pages":"Article 108166"},"PeriodicalIF":3.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007386","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}

引用次数: 0

Investigating the role of elastin and extracellular matrix damage in cardiovascular calcification 研究弹性蛋白和细胞外基质损伤在心血管钙化中的作用。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-03-01 Epub Date: 2024-12-04 DOI: 10.1016/j.jsb.2024.108140

Elham Radvar , Khushbu Mehta , Alexander D’Ambrosio , Giulia Mastroianni , Maisoon Al-Jawad , Molly M. Stevens , Alvaro Mata , Sherif Elsharkawy

引用次数: 0