Journal of structural biology最新文献_第6页

A structural perspective of transmembrane transport of zinc by ZnT and ZIP transporters ZnT和ZIP转运体对锌跨膜转运的结构研究

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-09-01 Epub Date: 2025-07-22 DOI: 10.1016/j.jsb.2025.108235

Qingrong Xie , Jiuyu Ding , Chunting Fu , Xi Chen , Ziyi Sun , Xiaoming Zhou

引用次数: 0

Characterization of NMDA receptor Allostery modulation NMDA受体变构调节的表征

IF 2.7 3区生物学

Journal of structural biology Pub Date : 2025-09-01 Epub Date: 2025-08-15 DOI: 10.1016/j.jsb.2025.108238

Yunsheng Liu , Wangsheng Song , Rongde Zhong , Jinfang Zhang , Xianlin Wu , Yanyan Jia , Zengwei Kou

{"title":"Characterization of NMDA receptor Allostery modulation","authors":"Yunsheng Liu , Wangsheng Song , Rongde Zhong , Jinfang Zhang , Xianlin Wu , Yanyan Jia , Zengwei Kou","doi":"10.1016/j.jsb.2025.108238","DOIUrl":"10.1016/j.jsb.2025.108238","url":null,"abstract":"<div><div>NMDA receptors are subject to numerous endogenous and exogenous allosteric regulations, which are essential for their complex pathophysiological functions in the brain, and serve as a basis for therapeutic targeting. However, the structural basis of many of these allosteric mechanisms remains unclear. In this study, we first utilized AlphaFold to predict the structural conformations of different NMDA receptor subtypes. Subsequent comparative analyses with experimentally resolved protein structures, coupled with validation using disulfide bond formation, revealed the high precision of these computational predictions. Based on these structures, we systematically investigated the allosteric regulation of NMDA receptors using RoseTTAFold-All-Atom. Our findings elucidated the binding sites of several allosteric modulators across different NMDA receptor subtypes and identified the key amino acids required for binding. These results reveal the structural basis of NMDA receptor allosteric regulation, providing new insights into its physiological and pathological roles, and offering potential avenues for drug development.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 3","pages":"Article 108238"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144866109","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 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 : 2025-09-01 Epub 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":"2025-09-01","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

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 : 2025-09-01 Epub 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":"2025-09-01","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 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 : 2025-09-01 Epub 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":"2025-09-01","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

Sequence/structural/functional relationships between Ganoderma fungal immunomodulatory proteins (gFIPs) and proteins involved in the modulation of immune response 灵芝真菌免疫调节蛋白（gFIPs）与免疫应答调节蛋白之间的序列/结构/功能关系

IF 2.7 3区生物学

Journal of structural biology Pub Date : 2025-09-01 Epub Date: 2025-08-13 DOI: 10.1016/j.jsb.2025.108237

Nikola Schlosserová , Giulia Chiara Maria Perrone , Jakub Treml , Maria Noemi Sgobba , Lorenzo Guerra , Ciro Leonardo Pierri

{"title":"Sequence/structural/functional relationships between Ganoderma fungal immunomodulatory proteins (gFIPs) and proteins involved in the modulation of immune response","authors":"Nikola Schlosserová , Giulia Chiara Maria Perrone , Jakub Treml , Maria Noemi Sgobba , Lorenzo Guerra , Ciro Leonardo Pierri","doi":"10.1016/j.jsb.2025.108237","DOIUrl":"10.1016/j.jsb.2025.108237","url":null,"abstract":"<div><div>Fungal Immunomodulatory Proteins from <em>Ganoderma</em> species (gFIPs) have garnered significant interest due to their potential therapeutic applications in modulating immune responses. This study investigates the sequence, structural, and functional relationships of gFIPs with other proteins involved in immune modulation. Utilizing molecular modelling, multiple sequence alignments, and structural superimposition, we analysed two FIP crystallized structures (PDB IDs: 3F3H and 3KCW) alongside homologous sequences from various taxonomic groups. Our results reveal conserved motifs across fungal, bacterial, and human sequences, indicating potential functional similarities. Comparative structural analysis highlights significant conservation in FIP architecture, with variations primarily in the N-terminal regions. Notably, structural alignment with bacterial toxins, such as ADP-ribosylating binary toxin from <em>Clostridium difficile</em> or protective antigen of Anthrax toxin from <em>Bacillus anthracis</em> suggests mechanistic insights into FIP’s immunomodulatory actions. Structural similarities between gFIPs and immune-related proteins, such as bacterial toxin-binding domains, antibody fragments, T-cell receptor components, and immune checkpoint regulators (PD-1) suggest their potential involvement in immune response/inflammation signalling pathways. This comprehensive analysis elucidates the structural basis for the diverse biological activities of gFIPs and underscores their potential as therapeutic agents in immune-related diseases.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 3","pages":"Article 108237"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859271","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

Molecular recognition and structural plasticity in amyloid–nucleic acid complexes 淀粉样蛋白-核酸复合物的分子识别和结构可塑性

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-09-01 Epub Date: 2025-07-14 DOI: 10.1016/j.jsb.2025.108233

Ritika Kukreja, Michael P. Latham

引用次数: 0

Insights into the pathogenic mechanisms associated with the SARS-CoV-2 spike protein 深入了解与SARS-CoV-2刺突蛋白相关的致病机制

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-09-01 Epub Date: 2025-06-23 DOI: 10.1016/j.jsb.2025.108229

Mia Argyrou , Eleni Pitsillou , Andrew Hung , Assam El-Osta , Tom C. Karagiannis

{"title":"Insights into the pathogenic mechanisms associated with the SARS-CoV-2 spike protein","authors":"Mia Argyrou , Eleni Pitsillou , Andrew Hung , Assam El-Osta , Tom C. Karagiannis","doi":"10.1016/j.jsb.2025.108229","DOIUrl":"10.1016/j.jsb.2025.108229","url":null,"abstract":"<div><div>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogenic agent responsible for the coronavirus disease 2019 (COVID-19) pandemic, uses the trimeric spike protein to gain entry into the host cell. Structural studies have revealed that the spike protein is comprised of the S1 and S2 subunits. The S1 subunit of the spike protein contains the receptor-binding domain (RBD), which binds to the human angiotensin-converting enzyme 2 (ACE2) receptor. The interaction between the RBD and ACE2 facilitates membrane fusion and host cell infection. The SARS-CoV-2 spike protein also contains a unique insertion of four amino acids that results in the 682-RRAR↓S-686 polybasic furin cleavage motif at the boundary of the S1 and S2 subunits. The furin cleavage motif contributes to the high infectivity and transmissibility of SARS-CoV-2. This review provides a comprehensive analysis of the molecular interactions of the spike protein, with a specific focus on the RBD and furin cleavage site. In addition to examining the binding characteristics with ACE2, the interactions with alternative receptors, such as neuropilin-1 (NRP1) and the nicotinic acetylcholine receptors (nAChRs) are highlighted. The ability of the spike protein to bind alternative receptors and host factors has been linked to the pathophysiology of COVID-19 and the persistence of symptoms in the post COVID-19 condition. Furthermore, we examine the impact of spike protein mutations on receptor affinity and disease severity. SARS-CoV-2 continues to evolve, with variants remaining an ongoing threat to public health. Understanding these molecular interactions is critical for the development of novel therapeutic interventions.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 3","pages":"Article 108229"},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144481082","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

Binding of an N protein peptide to M protein of a bat coronavirus 一种蝙蝠冠状病毒N蛋白肽与M蛋白的结合

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-09-01 Epub Date: 2025-07-13 DOI: 10.1016/j.jsb.2025.108234

Xiaodong Wang, Siqi Yang , Penghui Yang , Ziyi Sun, Xiaoming Zhou

引用次数: 0

Effects of base temperature, immersion medium, and EM grid material on devitrification thresholds in cryogenic optical super-resolution microscopy 基底温度、浸泡介质和EM栅格材料对低温光学超分辨显微镜反玻化阈值的影响

IF 3 3区生物学

Journal of structural biology Pub Date : 2025-09-01 Epub Date: 2025-07-17 DOI: 10.1016/j.jsb.2025.108231

Soheil Mojiri , Joseph M. Dobbs , Niko Faul , Thomas P. Burg , Julia Mahamid , Jonas Ries

{"title":"Effects of base temperature, immersion medium, and EM grid material on devitrification thresholds in cryogenic optical super-resolution microscopy","authors":"Soheil Mojiri , Joseph M. Dobbs , Niko Faul , Thomas P. Burg , Julia Mahamid , Jonas Ries","doi":"10.1016/j.jsb.2025.108231","DOIUrl":"10.1016/j.jsb.2025.108231","url":null,"abstract":"<div><div>Cryogenic correlative light and electron microscopy (cryo-CLEM) is an imaging strategy that integrates specific molecular labeling and molecular resolution structural information. However, there is a resolution gap of more than two orders of magnitude between diffraction-limited fluorescence microscopy and electron microscopy (EM). Single-molecule localization microscopy (SMLM) performed at cryogenic temperatures promises to bridge this resolution gap. Nevertheless, the high excitation laser powers required for SMLM risk the devitrification of frozen biological samples, leading to perturbation of their native-like state. Here, we investigate how base cooling temperature, immersion medium, and EM grid support materials influence sample devitrification. Using finite element simulations and experimental validation, we show that a cryo-immersion medium enhances heat dissipation for carbon supports, while metallic supports in a cold nitrogen gas medium tolerate higher laser intensities due to lower base temperatures. Gold supports illuminated at <span><math><mrow><mn>640</mn><mspace></mspace><mi>nm</mi></mrow></math></span> exhibit markedly high laser thresholds, similar to silver-coated grids. Additionally, metallic supports maintain efficient heat dissipation in vacuum-based cryostats. Our findings provide quantitative insights that aid in optimization of cryo-SMLM setups for improved cryo-CLEM imaging.</div></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":"217 3","pages":"Article 108231"},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144665781","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