Journal of Molecular Biology最新文献_第6页

Rising Star: Lysosomes as Dead Cell Buriers and Key Guardians of Organismal Homeostasis 冉冉升起的新星：溶酶体作为死细胞的埋葬者和生物体动态平衡的关键守护者。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-09-01 DOI: 10.1016/j.jmb.2025.169408

Xiaochen Wang

{"title":"Rising Star: Lysosomes as Dead Cell Buriers and Key Guardians of Organismal Homeostasis","authors":"Xiaochen Wang","doi":"10.1016/j.jmb.2025.169408","DOIUrl":"10.1016/j.jmb.2025.169408","url":null,"abstract":"<div><div>Xiaochen Wang studied plant biology as a Ph.D. student at Peking University, China, and worked on programmed cell death as a post-doctoral fellow at University of Colorado at Boulder. Wang set up her own research group to initially investigate the clearance of apoptotic cells by lysosomes and later redirected her research to decipher lysosome dynamics and functions in a multicellular organism. Lysosomes are major degradative organelles and signaling centers in the cell that play important roles in a wide variety of processes to maintain cell and tissue homeostasis. Lysosome dysfunction is associated with metabolic disorders, neurodegenerative diseases, and age-related pathologies. As the burier of dead cells, lysosomes degrade apoptotic cells delivered via phagocytosis to enable a safe funeral without stimulating inflammatory responses. The Wang lab has systematically dissected the regulatory pathways by which apoptotic cells are recognized and engulfed by phagocytes, and delivered to and digested by lysosomes. Intrigued by the highly changeable morphology and versatile functions of lysosomes, Wang and colleagues developed <em>C. elegans</em> as a multicellular model to investigate how lysosome dynamics and functions are regulated to maintain animal development and longevity.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 21","pages":"Article 169408"},"PeriodicalIF":4.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

McsB Regulates CtsR Thermosensing Through Peripheral Arginine Phosphorylation McsB通过外周精氨酸磷酸化调节CtsR的热感。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-30 DOI: 10.1016/j.jmb.2025.169409

Huahuan Cai , Boyang Hua , Jie Hu , Yiben Fu , Shuting Liu , Xinlei Ding , Gege Duan , Yeting Guo , Xing-Hua Xia , Yufen Zhao

{"title":"McsB Regulates CtsR Thermosensing Through Peripheral Arginine Phosphorylation","authors":"Huahuan Cai , Boyang Hua , Jie Hu , Yiben Fu , Shuting Liu , Xinlei Ding , Gege Duan , Yeting Guo , Xing-Hua Xia , Yufen Zhao","doi":"10.1016/j.jmb.2025.169409","DOIUrl":"10.1016/j.jmb.2025.169409","url":null,"abstract":"<div><div>When cells sense an elevated temperature in the environment, the bacterial master transcription repressor CtsR becomes phosphorylated and inactivated by the arginine kinase McsB to initiate the expression of heat-shock genes. Here, we utilize a fluorescence intensity shift assay (FISA) based on the <strong><em><u>p</u></em></strong>hoto<strong><em><u>i</u></em></strong>somerisation-related <strong><em><u>f</u></em></strong>luorescence <strong><em><u>e</u></em></strong>nhancement (or previously protein-induced fluorescence enhancement, PIFE) effect to monitor the DNA-CtsR-McsB interactions in real time. Our single-molecule analysis reveals that CtsR binds rapidly and stably to the cognate DNA, and that McsB is able to transiently interact with CtsR <em>in situ</em> of the target DNA. We determine the binding kinetics between McsB and the DNA-bound CtsR by single-molecule real-time binding assays, with <em>k<sub>on</sub></em> and <em>k<sub>off</sub></em> of 0.75 μM<sup>−1</sup> s<sup>−1</sup> and 0.34 s<sup>−1</sup>, respectively. This interaction with McsB does not remove CtsR from the DNA, but lowers the temperature threshold for CtsR dissociation and alters its thermosensing behavior. Mass spectrometry, mutational analysis and structural simulation results together suggest that the phosphorylation of several peripheral arginine residues on CtsR, which reduces the binding energy of the CtsR-DNA complex, underlies a plausible molecular mechanism for this effect. Taken together, these results provide insights into how McsB regulates the CtsR-DNA interaction and highlight the functional importance of CtsR peripheral arginine residues in the bacterial heat-shock response.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 21","pages":"Article 169409"},"PeriodicalIF":4.5,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

FoldExplorer: Fast and Accurate Protein Structure Search with Sequence-Enhanced Graph Embedding FoldExplorer：快速和准确的蛋白质结构搜索与序列增强图嵌入。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-30 DOI: 10.1016/j.jmb.2025.169412

Yuan Liu, Ying Zhang, Zhen Zhou, Hong-Bin Shen

{"title":"FoldExplorer: Fast and Accurate Protein Structure Search with Sequence-Enhanced Graph Embedding","authors":"Yuan Liu, Ying Zhang, Zhen Zhou, Hong-Bin Shen","doi":"10.1016/j.jmb.2025.169412","DOIUrl":"10.1016/j.jmb.2025.169412","url":null,"abstract":"<div><div>The advent of highly accurate protein structure prediction methods has fueled an exponential expansion of the protein structure database. Consequently, there is a rising demand for rapid and precise protein structure search. Traditional alignment-based methods are designed for precise pairwise comparisons, offering high accuracy. However, they face challenges when searching within large databases. In response to this challenge, we propose a novel deep-learning approach FoldExplorer. It leverages graph attention neural networks and protein language models to jointly encode structural and sequence information, generating embeddings tailored for protein structure search. FoldExplorer achieves competitive performance in geometric similarity search and classification tasks, outperforming recent deep learning and sequence-based methods, and approaching classical alignment tools. Significantly, FoldExplorer remains effective when searching low-confidence predicted structures. Meanwhile, FoldExplorer is particularly highly efficient when searching in large-scale databases. The accurate embedding space generated by FoldExplorer enables providing a comprehensive protein structure space view, which will provide novel cluster and boundary insights on the protein universe studies. A publicly accessible search web server is available at: <span><span>http://www.csbio.sjtu.edu.cn/bioinf/FoldExplorer/</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 21","pages":"Article 169412"},"PeriodicalIF":4.5,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Dynamic Interactions in the Human β₁AR Signalling Complex with Mini-G_s Revealed by NMR. 人β1AR信号复合物与mini-Gs的动态相互作用。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-30 DOI: 10.1016/j.jmb.2025.169411

Philip Rößler, Marco M Ruckstuhl, Arnelle Löbbert, Timo T Stühlinger, Ching-Ju Tsai, Gebhard F X Schertler, Alvar D Gossert

{"title":"Dynamic Interactions in the Human β<sub>1</sub>AR Signalling Complex with Mini-G<sub>s</sub> Revealed by NMR.","authors":"Philip Rößler, Marco M Ruckstuhl, Arnelle Löbbert, Timo T Stühlinger, Ching-Ju Tsai, Gebhard F X Schertler, Alvar D Gossert","doi":"10.1016/j.jmb.2025.169411","DOIUrl":"10.1016/j.jmb.2025.169411","url":null,"abstract":"<p><p>A wealth of insights into the mechanisms of GPCRs have been gained from biophysical studies of thermostabilized β<sub>1</sub> adrenergic receptors (β<sub>1</sub>AR) from turkey. Here we investigate a stabilised variant of the pharmacologically more relevant human β<sub>1</sub>AR and present initial insights into the active signalling complex with the G protein surrogate mini-G<sub>s</sub>. Compared to the avian receptor, the human β<sub>1</sub>AR construct exhibits greater conformational flexibility and more readily transitions between inactive and pre-active states; however, the transition to the fully active, open state remains slow. Interestingly, in contrast, the bound mini-G<sub>s</sub> protein exhibits much faster dynamics in the ternary complex. For the receptor in the signalling complex, we reveal at least two interconverting states of intracellular loop 2 and the extracellular end of transmembrane helix 1. Additionally, we demonstrate that intracellular loop 3 contributes to mini-G<sub>s</sub> binding. This human β<sub>1</sub>AR construct provides a valuable platform for biophysical studies at the atomic level towards understanding the behaviour of the human receptor.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169411"},"PeriodicalIF":4.5,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Allostery in Disease: From Mutations, Mechanisms, and Signalling Partners to Diagnostic and Drug Therapies 疾病变构：从突变、机制和信号伙伴到诊断和药物治疗。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-22 DOI: 10.1016/j.jmb.2025.169407

Igor N. Berezovsky , Ruth Nussinov

引用次数: 0

Cryo-EM exposes diverse polymorphism in IAPP mutants to guide the rational design of peptide-based therapeutics Cryo-EM揭示了IAPP突变体的多种多态性，以指导基于肽的治疗方法的合理设计。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-22 DOI: 10.1016/j.jmb.2025.169405

Saik Ann Ooi , Dylan Valli , Mikołaj I. Kuska , Helena Marí , Himanshu Chaudhary , Weixiao Yuan Wahlgren , Sebastian Westenhoff , Alesia A. Tietze , Anna Novials , Joan-Marc Servitja , Michał Maj

{"title":"Cryo-EM exposes diverse polymorphism in IAPP mutants to guide the rational design of peptide-based therapeutics","authors":"Saik Ann Ooi , Dylan Valli , Mikołaj I. Kuska , Helena Marí , Himanshu Chaudhary , Weixiao Yuan Wahlgren , Sebastian Westenhoff , Alesia A. Tietze , Anna Novials , Joan-Marc Servitja , Michał Maj","doi":"10.1016/j.jmb.2025.169405","DOIUrl":"10.1016/j.jmb.2025.169405","url":null,"abstract":"<div><div>In the pursuit of potential therapeutic agents for type 2 diabetes, non-amyloidogenic forms of the human Islet Amyloid Polypeptide (hIAPP) containing site-specific mutations are of significant interest. In the present study, we dissect the three proline mutations present in the core region of the non-amyloidogenic rat IAPP into single-point mutations at A25P, S28P, and S29P sites. We apply high-resolution cryo-electron microscopy and solve the structures of 6 polymorphs formed by these mutants, revealing the peptide’s self-assembly patterns and identifying critical interactions that reinforce these structures in the presence of the <span><math><mrow><mi>β</mi></mrow></math></span>-sheet breaker. A unique trimeric aggregate with C3 symmetry was identified in the A25P mutant, which we resolved with a 3.05 Å resolution, while asymmetric trimeric assemblies were observed in the other mutants. Guided by the high-resolution structural models of A25P and S28P fibrils obtained in our study, we successfully designed novel non-amyloidogenic mutants of IAPP with potential therapeutic value. Our findings demonstrate the immense potential of structure-based approaches in developing effective therapeutics against amyloid diseases.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 21","pages":"Article 169405"},"PeriodicalIF":4.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Application of NMR to Large RNAs. 核磁共振在大rna中的应用。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-22 DOI: 10.1016/j.jmb.2025.169406

Brian D Grossman, Jan Marchant, Michael F Summers

引用次数: 0

Conformational Changes in Type IA Topoisomerases Facilitate Strand Passage. IA型拓扑异构酶的构象改变促进了链的通过。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-21 DOI: 10.1016/j.jmb.2025.169402

Deepesh Sigdel, Dillon Balthrop, Maria Mills

引用次数: 0

Impact of Horizontal Gene Transfer on Adaptations to Extreme Environments. 水平基因转移对极端环境适应的影响。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-21 DOI: 10.1016/j.jmb.2025.169403

Olga Zhaxybayeva, Camilla L Nesbø

{"title":"Impact of Horizontal Gene Transfer on Adaptations to Extreme Environments.","authors":"Olga Zhaxybayeva, Camilla L Nesbø","doi":"10.1016/j.jmb.2025.169403","DOIUrl":"10.1016/j.jmb.2025.169403","url":null,"abstract":"<p><p>Horizontal (or lateral) gene transfer - an acquisition of genetic material not associated with the organismal reproduction - is known to alter genomes of most, if not all, living organisms. There is mounting evidence for the importance of gene exchange in organismal adaptations to new or changing environmental conditions. In comparison to accumulation of de novo mutations, acquisition of a gene already beneficial in the environment is fast and less costly, and thus an advantageous, way to adjust to survival and growth in new conditions. Adaptation to extreme environments at the boundaries of habitat conditions beyond which cellular integrity, metabolism and growth are not possible, is not an exception. Here we review the impact of horizontal gene transfer on organismal adaptations to natural and human-made extreme environments. This includes thermophiles living at high temperatures, psychrophiles found at low temperatures, acidophiles inhabiting high acidity environments, alkaliphiles thriving at high pH, halophiles found in high salt environments, xerophiles that can tolerate extremely low water availability, oligotrophes thriving at low nutrient availability, piezophiles inhabiting high pressure environments, and organisms that can withstand high levels of ionizing radiation. We also discuss the challenges and future directions for deciphering genetic determinants and horizontal gene transfer events of extremophiles' adaptations.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169403"},"PeriodicalIF":4.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Generation of a Recombinant Mimivirus by Homologous Recombination Using Direct Transfection of a PCR Amplicon 用PCR扩增子直接转染同源重组产生重组mimivirus。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2025-08-21 DOI: 10.1016/j.jmb.2025.169404

Hiroyuki Hikida, Hiroyuki Ogata

引用次数: 0