Journal of structural biology最新文献

The product specificities of terpinolene synthase, from cannabis sativa, reveals the plasticity of the terpene synthase active site 从大麻中提取的萜烯合成酶的产物特异性揭示了萜烯合成酶活性位点的可塑性

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-06-18 DOI: 10.1016/j.jsb.2025.108227

Danielle Wiles , James Roest , Julian P. Vivan , Travis Beddoe

{"title":"The product specificities of terpinolene synthase, from cannabis sativa, reveals the plasticity of the terpene synthase active site","authors":"Danielle Wiles , James Roest , Julian P. Vivan , Travis Beddoe","doi":"10.1016/j.jsb.2025.108227","DOIUrl":"10.1016/j.jsb.2025.108227","url":null,"abstract":"<div><div><em>Cannabis sativa</em> is a high-value plant renowned for its diverse chemical composition and abundant terpene content, contributing to its unique aroma, flavour, and therapeutic effects. Terpenes significantly influence consumer preference for <em>C. sativa</em> products, driving scientific interest in optimising terpene expression profiles and shaping the selective breeding of terpene profiles in <em>C. sativa</em> cultivars. In particular, the monoterpene, terpinolene, is influential in defining the sensory and therapeutic qualities of many <em>C. sativa</em> strains due to its woody, citrus-like aroma. Here we report the 2.5 Å resolution crystal structure of terpinolene synthase (CsTOS) from C. <em>sativa</em> in its apo form. The structure exhibits the class I monoterpene synthase fold with an open active site conformation. Using site-directed mutagenesis, we identified H618 as a key residues in determining product specificity. Substituting H618 with charged residues resulted in the preferential formation of limonene over terpinolene, highlighting its critical role in stabilising the substrate intermediate. Additionally, novel mutations uncovered an extended epistatic network of residues within 5 Å of the active site, spanning the α-helical bundle of the terpene synthase fold. These interactions contribute to monoterpene formation by modulating substrate positioning and catalytic activity. These insights advance our understanding of monoterpene biosynthesis and enable the targeted engineering of terpene synthases for customised terpene production, offering significant potential for the <em>C. sativa</em> industry.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 3","pages":"Article 108227"},"PeriodicalIF":3.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144321669","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

Structural insights into human adenylyl cyclase 9 in complex with Gαs by cryo-EM 人腺苷酸环化酶9与Gαs复合物的结构分析

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-06-02 DOI: 10.1016/j.jsb.2025.108223

Risa Nomura , Shota Suzuki , Koki Nishikawa , Hiroshi Suzuki , Yoshinori Fujiyoshi

{"title":"Structural insights into human adenylyl cyclase 9 in complex with Gαs by cryo-EM","authors":"Risa Nomura , Shota Suzuki , Koki Nishikawa , Hiroshi Suzuki , Yoshinori Fujiyoshi","doi":"10.1016/j.jsb.2025.108223","DOIUrl":"10.1016/j.jsb.2025.108223","url":null,"abstract":"<div><div>Adenylyl cyclase 9 (AC9) regulates many physiologic functions through the production of cAMP, an important second messenger that regulates downstream effectors. The activation of AC9 is highly regulated by GPCR signaling. For example, AC9 is activated by the binding of Gαs, which, in turn, is activated by Gs-driven GPCRs. The structure of bovine AC9 (bAC9) was reported in 2019 using single-particle cryo-electron microscopy (cryo-EM). The structure of human AC9 (hAC9), however, has not been reported to date despite its potential benefit for drug development. Here, we analyzed the structures of hAC9 and hAC9 in complex with Gαs (hAC9-Gαs) using single-particle cryo-EM. The soluble domain of AC9-Gαs, the transmembrane (TM) domain of AC9-Gαs, and AC9 alone were analyzed at resolutions of 2.7 Å, 3.4 Å, and 3.2 Å, respectively. The results revealed three key aspects of the activation mechanism of hAC9 and its cAMP-generating function. First, a conformational change of the soluble domain was observed upon Gαs binding, resulting in a widely open catalytic site. Second, we analyzed the exact position of the C-terminus occluding the catalytic site in the hAC9-Gαs complex. Finally, we unexpectedly identified an elongated density suggestive of a single acyl chain in the TM domain. Consistent with recent reports on the allosteric regulation of AC by lipids, this finding suggests that the TM domain could serve as a potential drug target.These structural findings enhance our understanding of the structure and function of AC9 and other ACs and will provide a foundation for future AC-target drug discovery.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 3","pages":"Article 108223"},"PeriodicalIF":3.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144196126","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 generalist deep-learning volume segmentation tool for volume electron microscopy of biological samples 一个通用的深度学习体积分割工具，用于生物样品的体积电子显微镜。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-05-29 DOI: 10.1016/j.jsb.2025.108214

Yuyao Huang , Nickhil Jadav , Georgia Rutter , Lech Szymanski , Mihnea Bostina , Duane P. Harland

引用次数: 0

ArtiaX: geometric models, camera paths and image processing tools ArtiaX：几何模型，相机路径和图像处理工具。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-05-28 DOI: 10.1016/j.jsb.2025.108215

Pauline Roth , Utz H. Ermel , Deborah Moser , Gunnar Arctaedius , Maren Wehrheim , Margot P. Scheffer , Achilleas S. Frangakis

{"title":"ArtiaX: geometric models, camera paths and image processing tools","authors":"Pauline Roth , Utz H. Ermel , Deborah Moser , Gunnar Arctaedius , Maren Wehrheim , Margot P. Scheffer , Achilleas S. Frangakis","doi":"10.1016/j.jsb.2025.108215","DOIUrl":"10.1016/j.jsb.2025.108215","url":null,"abstract":"<div><div>Biomolecular image analysis and data interpretation is significantly improved through the application of advanced visualization techniques. Numerous visualization packages are currently available, spanning a broad spectrum of applications. Recently, we developed a plugin called ArtiaX which extended the capabilities of UCSF ChimeraX to address the specific demands of cryo-electron tomography. Here, we introduce the evolution of ArtiaX, that can now generate models to facilitate particle selection, define camera recording paths, and execute particle selection routines. Diverse models can be generated and populated with putative particle positions and orientations. In addition, models can be used to drive the camera position, thereby simplifying the process of movie creation. The plugin incorporates fundamental image filtering options for the on-the-fly analysis of tomographic data and provides compatibility of particle lists with RELION-5 .star files. Collectively, this update of ArtiaX comprehensively encompasses essential tools for the analysis and visualization of electron tomograms. It retains its hallmark attributes of speed, reliability, and user-friendliness, fostering seamless human–machine interaction.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 3","pages":"Article 108215"},"PeriodicalIF":3.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187251","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

Structural insights into substrate recognition of tri-modular xyloglucanase from Aspergillus oryzae 米曲霉三模木糖葡聚糖酶底物识别的结构研究。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-05-23 DOI: 10.1016/j.jsb.2025.108213

Yusuke Nakamichi , Naoki Shimada , Masahiro Watanabe , Tatsuya Fujii , Katsuro Yaoi , Tomohiko Matsuzawa

引用次数: 0

Structural and biophysical characterization of PadR family protein Rv0047c of Mycobacterium tuberculosis H37Rv 结核分枝杆菌H37Rv PadR家族蛋白Rv0047c的结构与生物物理特性

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-05-20 DOI: 10.1016/j.jsb.2025.108211

Md Samsuddin Ansari , Muhammad Zohib , Meera Kumari , Vikash Yadav , Ravi Kant Pal , Sarita Tripathi , Anupam Jain , Bichitra Kumar Biswal , Ashish Arora

{"title":"Structural and biophysical characterization of PadR family protein Rv0047c of Mycobacterium tuberculosis H37Rv","authors":"Md Samsuddin Ansari , Muhammad Zohib , Meera Kumari , Vikash Yadav , Ravi Kant Pal , Sarita Tripathi , Anupam Jain , Bichitra Kumar Biswal , Ashish Arora","doi":"10.1016/j.jsb.2025.108211","DOIUrl":"10.1016/j.jsb.2025.108211","url":null,"abstract":"<div><div>The members of the PadR family of transcriptional regulators are important for cell survival in toxic environments and play an important role in detoxification, pathogenicity, and multi-drug resistance. Rv0047c of <em>Mycobacterium tuberculosis</em> H37Rv is annotated as a PadR family protein. We have characterized the stability and structure of Rv0047c. Rv0047c forms a stable dimer in solution. Its stability is characterized by a thermal melting transition temperature (Tm) of 55.3 °C. The crystal structure of Rv0047c was determined at a resolution of 3.15 Å. The structure indicates the biological unit to be a dimer with each monomer having a characteristic N-terminal winged-helix-turn-helix DNA binding domain and a C-terminal dimerization domain. The N-terminal domain is composed of four helices, α1, α2, α3, and α4 and two beta strands β1 and β2. The C-terminal dimerization domain (CTD) consists two long helices α6 and α7. The two domains are connected by helix α5. A short helical turn (helix αa, residue 89–92), leads to compaction of the α4-α5 loop. Rv0047c exhibits specificity in binding to an upstream region having an inverted repeat sequence. This binding is dependent upon Y18 and Y40 residue of Rv0047c, which are highly conserved among the PadR family. Overall, our results suggest a transcription regulatory role for Rv0047c, similar to other PadR family proteins.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 2","pages":"Article 108211"},"PeriodicalIF":3.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127989","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

The mechanism underlying fascin-mediated bundling of actin filaments unveiled by cryo-electron tomography 冷冻电子断层扫描揭示了肌动蛋白纤维束化的机制

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-05-20 DOI: 10.1016/j.jsb.2025.108212

Xiyong Song , Jesús Baltanás-Copado , Muniyandi Selvaraj , Shrikant B. Kokate , Esa-Pekka Kumpula , Senena Corbalán-García , Juha T. Huiskonen

{"title":"The mechanism underlying fascin-mediated bundling of actin filaments unveiled by cryo-electron tomography","authors":"Xiyong Song , Jesús Baltanás-Copado , Muniyandi Selvaraj , Shrikant B. Kokate , Esa-Pekka Kumpula , Senena Corbalán-García , 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":"2025-05-20","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}

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 : 2025-05-16 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":"2025-05-16","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

Calcium carbonate deposition in the spicules of the sponge Heteropia glomerosa (Porifera, Calcarea) 海绵小球异视（Porifera, Calcarea）的针状物中的碳酸钙沉积。

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-05-14 DOI: 10.1016/j.jsb.2025.108210

Camila Wendt , Fernanda C. de Medeiros , Raquel P. Gonçalves , Fabio Nudelman , Michelle Klautau , Marcos Farina , André L. Rossi

{"title":"Calcium carbonate deposition in the spicules of the sponge Heteropia glomerosa (Porifera, Calcarea)","authors":"Camila Wendt , Fernanda C. de Medeiros , Raquel P. Gonçalves , Fabio Nudelman , Michelle Klautau , Marcos Farina , 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":"2025-05-14","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}

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 : 2025-05-14 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":"2025-05-14","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