Journal of Molecular Biology最新文献

Science in the U.S. Is Under Attack – What Can We Do? 美国的科学受到攻击——我们能做些什么？

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-04-22 DOI: 10.1016/j.jmb.2025.169165

引用次数: 0

Unraveling a Receptor-Mediated Bioluminescence Signaling Pathway in Red Tide Algae 揭示赤潮藻中受体介导的生物发光信号通路

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-04-12 DOI: 10.1016/j.jmb.2025.169153

Aidan McFarland , Malissa Fenton , Jesper J. Madsen , Libin Ye

{"title":"Unraveling a Receptor-Mediated Bioluminescence Signaling Pathway in Red Tide Algae","authors":"Aidan McFarland , Malissa Fenton , Jesper J. Madsen , Libin Ye","doi":"10.1016/j.jmb.2025.169153","DOIUrl":"10.1016/j.jmb.2025.169153","url":null,"abstract":"<div><div>G protein-coupled receptors (GPCRs) are ubiquitous transmembrane proteins in multicellular life. Human vision, taste, and neuron activity are all mediated by GPCRs, and a large percentage of currently approved drugs target GPCRs. However, our understanding of GPCRs in single-celled eukaryotes is incomplete, and many of the components of GPCR signal transduction are underrepresented in protists. Previous works studying bioluminescent dinoflagellates—single-celled algae involved in coral reef endosymbiosis and toxic red tide blooms—implicate GPCRs in a signaling pathway for bioluminescence but have not elucidated the individual components comprising the pathway. Herein, we identified a novel GPCR in dinoflagellates—Bioluminescence-Inducing Receptor 1 (BIR1)—which plays a significant role in the signaling pathway for bioluminescence in red tide blooms in response to wave turbulence. Additionally, we identified a full endogenous G-protein complex and downstream effectors that are integral to known calcium signaling networks. Based on these identifications, we used knockdown and knockout techniques to demonstrate the integral role of BIR1 in bioluminescence and highlight its role in predator response and shear force-elicited GPCR signaling in red tide blooms. This advance opens avenues for red tide control and supports the existence of similar GPCR pathways involved in bloom toxicity dynamics.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 13","pages":"Article 169153"},"PeriodicalIF":4.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143868992","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

PLK4 Homodimerization is Required for CEP152 Centrosome Localization and Spindle Organization PLK4同二聚化是CEP152中心体定位和纺锤体组织所必需的

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-04-11 DOI: 10.1016/j.jmb.2025.169152

Harshita Kasera, Srishti Sanghi, Priyanka Singh

{"title":"PLK4 Homodimerization is Required for CEP152 Centrosome Localization and Spindle Organization","authors":"Harshita Kasera, Srishti Sanghi, Priyanka Singh","doi":"10.1016/j.jmb.2025.169152","DOIUrl":"10.1016/j.jmb.2025.169152","url":null,"abstract":"<div><div>The centrosome-specific Polo-Like Kinase 4 (PLK4) is a unique serine/threonine kinase family member that homodimerizes using its cryptic polo-box (CPB) region. PLK4 homodimerization causes transphosphorylation, which activates its ubiquitin-mediated degradation. The same CPB interacts with upstream centrosome recruiters, CEP152 and CEP192 in human cells. However, the involvement of PLK4 homodimerization with the CEP192-CEP152 network remains unexplored. This work identified a cancerous PLK4 variant, which truncated the protein to disrupt the CPB at 774 residue. The truncated PLK4 is unable to homodimerize or interact with CEP152 or CEP192. During the S-phase, CEP152 recruits PLK4 to centrosomes, and the homodimerization of PLK4 is needed to maintain CEP152 at centrosomes. The reduction in levels of CEP152 on PLK4 homodimerization mutant expression correlates to pericentrin at S-phase centrosomes, which causes unfocussed spindles at the M-phase and reduces cell viability. The work shows a cross-dependency between CEP152 and PLK4 homodimerization for centrosome functioning, which is disrupted in cancer.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 13","pages":"Article 169152"},"PeriodicalIF":4.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873944","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

Membrane Modification and Adaptation of Metabolism by Acinetobacter baumannii Prompts Resistance to Antimicrobial Activity of Outer Membrane Perturbing Peptide L8 鲍曼不动杆菌的膜修饰和代谢适应促进了外膜扰动肽L8的耐药性

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-04-11 DOI: 10.1016/j.jmb.2025.169135

Gina Schouten , Felix Paulussen , Tom N. Grossmann , Wilbert Bitter , Peter van Ulsen

{"title":"Membrane Modification and Adaptation of Metabolism by Acinetobacter baumannii Prompts Resistance to Antimicrobial Activity of Outer Membrane Perturbing Peptide L8","authors":"Gina Schouten , Felix Paulussen , Tom N. Grossmann , Wilbert Bitter , Peter van Ulsen","doi":"10.1016/j.jmb.2025.169135","DOIUrl":"10.1016/j.jmb.2025.169135","url":null,"abstract":"<div><div>Multidrug resistant (MDR) <em>Acinetobacter baumannii</em> has emerged as one of the most concerning nosocomial pathogens worldwide. One approach to target MDR <em>A. baumannii</em> is treatment with synergistic combinations of outer membrane-permeabilizing antimicrobial peptides (AMP) and antibiotics that otherwise only act against Gram-positive bacteria. Resistance against AMPs is rarely observed, especially when administered in combination with other drugs. Recently, we described the synergistic antimicrobial activity of AMPs L8 and L8S1 with rifampicin against a clinical isolate of <em>A. baumannii</em>. In the current work we explore the mechanisms of action of these peptides. We demonstrate that L8 and L8S1 perturb the cell envelope of <em>A. baumannii</em>. Moreover, we show that resistance against peptide L8 could be acquired <em>in vitro</em> either by increasing the amount of PE lipid on the surface or by increasing biofilm formation. Interestingly, the resistance to the antimicrobial activity of the peptides did not affect membrane perturbation or synergistic activity of the peptides with rifampicin, suggesting a dual mechanism of action for these peptides.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 13","pages":"Article 169135"},"PeriodicalIF":4.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873943","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

A pH-Centric Model of Nucleolar Activity and Regulation 一个以ph为中心的核仁活性和调控模型

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-04-10 DOI: 10.1016/j.jmb.2025.169136

Diego Detrés , Adriana Camacho-Badillo , Eliezer Calo

引用次数: 0

Essential Roles of Conserved Pseudouridines in Helix 69 for Ribosome Dynamics in Translation 螺旋69中保守假尿嘧啶在核糖体翻译动力学中的重要作用。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-04-05 DOI: 10.1016/j.jmb.2025.169132

Xin Chen , Hong Jin

{"title":"Essential Roles of Conserved Pseudouridines in Helix 69 for Ribosome Dynamics in Translation","authors":"Xin Chen , Hong Jin","doi":"10.1016/j.jmb.2025.169132","DOIUrl":"10.1016/j.jmb.2025.169132","url":null,"abstract":"<div><div>The widespread distribution of pseudouridine (Ψ), an isomer of the canonical uridine base, in RNA indicates its functional importance to the cell. In eukaryotes, it is estimated that around 2% of ribosomal RNA nucleotides are pseudouridines, most of which are located in functional regions of the ribosome. Defects in RNA pseudouridylation induce a range of detrimental effects from compromised cellular protein biosynthesis to disease phenotypes in humans. However, genome-wide changes to mRNA translation profiles by ribosomes lacking specific conserved pseudouridines have not been extensively studied. Here, using a new genomic method called 5PSeq and <em>in vitro</em> biochemistry, we investigated changes in ribosome dynamics and cellular translation profiles upon loss of Ψ2258 and Ψ2260 in helix 69, the two most conserved pseudouridines in the ribosome in yeast cells. We found that inhibiting the formation of these two pseudouridines challenges ribosomes to maintain the correct open reading frame and causes generally faster ribosome dynamics in translation. Furthermore, mutant ribosomes are more prone to pause while translating a subset of GC-rich codons, especially rare codons such as Arg (CGA) and Arg (CGG). These results demonstrate the presence of Ψ2258 and Ψ2260 contributes to the dynamics of the H69 RNA stem-loop, and helps to maintain functional interactions with the tRNAs as they move within the ribosome. The optimality of this ribosome-tRNA interaction is likely to be more critical for those limited tRNAs that decode rare codons. Consistent with the changes in ribosome dynamics, we observe that IRES-mediated translation is compromised in the mutant ribosome. These results explain the importance of Ψ2258 and Ψ2260 in H69 to maintain cellular fitness. The strong conservation of Ψ2258 and Ψ2260 in the ribosomes from bacteria to humans indicates their functional significance in modulating ribosome functions. It's likely that the identified functions of these covalent modifications are conserved across species.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 14","pages":"Article 169132"},"PeriodicalIF":4.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802128","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

ENsiRNA: A Multimodality Method for siRNA-mRNA and Modified siRNA Efficacy Prediction Based on Geometric Graph Neural Network ENsiRNA：一种基于几何图神经网络的siRNA- mrna和改良siRNA疗效预测的多模态方法。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-04-05 DOI: 10.1016/j.jmb.2025.169131

Wenchong Tan , Mingshu Dai , Shimin Ye , Xin Tang , Dawei Jiang , Dong Chen , Hongli Du

{"title":"ENsiRNA: A Multimodality Method for siRNA-mRNA and Modified siRNA Efficacy Prediction Based on Geometric Graph Neural Network","authors":"Wenchong Tan , Mingshu Dai , Shimin Ye , Xin Tang , Dawei Jiang , Dong Chen , Hongli Du","doi":"10.1016/j.jmb.2025.169131","DOIUrl":"10.1016/j.jmb.2025.169131","url":null,"abstract":"<div><div>With the rise of small interfering RNA (siRNA) as a therapeutic tool, effective siRNA design is crucial. Current methods often emphasize sequence-related features, overlooking structural information. To address this, we introduce ENsiRNA, a multimodal approach utilizing a geometric graph neural network to predict the efficacy of both standard and modified siRNA. ENsiRNA integrates sequence features from a pretrained RNA language model, structural characteristics, and thermodynamic data or chemical modifications to enhance prediction accuracy. Our results indicate that ENsiRNA outperforms existing methods, achieving over a 13% improvement in Pearson Correlation Coefficient (PCC) for standard siRNA across various tests. For modified siRNA, despite challenges associated with RNA folding methods, ENsiRNA still demonstrates competitive performance in different datasets. This novel method highlights the significance of structural information and multimodal strategies in siRNA prediction, advancing the field of therapeutic design.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"437 12","pages":"Article 169131"},"PeriodicalIF":4.7,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802123","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

Corrigendum to “Prion Propagation is Dependent on Key Amino Acids in Charge Cluster 2 within the Prion Protein” [J. Mol. Biol. 435(4) (2023) 167925] “朊病毒的繁殖依赖于朊病毒蛋白中负责簇2中的关键氨基酸”的更正[J]。生物化学学报。435(4)(2023)167925 [j]

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-04-05 DOI: 10.1016/j.jmb.2025.169114

Savroop Bhamra , Parineeta Arora , Szymon W. Manka, Christian Schmidt, Craig Brown, Melissa L.D. Rayner, Peter-Christian Klöhn, Anthony R. Clarke , John Collinge , Parmjit S. Jat

引用次数: 0

gmx_RRCS: a precision tool for detecting subtle conformational dynamics in molecular simulations. gmx_RRCS：在分子模拟中检测细微构象动力学的精密工具。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-04-04 DOI: 10.1016/j.jmb.2025.169129

Wei Han, Zhenghan Chen, Ming-Wei Wang, Qingtong Zhou

{"title":"gmx_RRCS: a precision tool for detecting subtle conformational dynamics in molecular simulations.","authors":"Wei Han, Zhenghan Chen, Ming-Wei Wang, Qingtong Zhou","doi":"10.1016/j.jmb.2025.169129","DOIUrl":"https://doi.org/10.1016/j.jmb.2025.169129","url":null,"abstract":"<p><p>Understanding conformational changes in biomolecules is crucial for insights into their biological functions and drug design, often studied by molecular dynamics (MD) simulations. However, current measurements such as RMSD, RMSF, interface area, and minimum distances fail to capture subtle conformational changes, including hydrophobic packing. Our study introduces gmx_RRCS, a precision tool developed to detect subtle conformational dynamics in MD simulations by analyzing residue-residue contact scores (RRCS). This tool quantifies interaction strengths between residues, enabling systematic analysis of both major and subtle conformational changes. Its application in investigating the molecular recognition of peptide 20 by glucagon-like peptide-1 receptor quantified the interactions of specific peptide moieties with the receptor, identified crucial positions for receptor binding, and highlighted key receptor residues involved in peptide recognition throughout the MD simulation. In phosphoinositide 3-kinase alpha (PI3Kα), gmx_RRCS revealed distinct conformational states of oncogenic hotspot residues by quantifying subtle sidechain reorientations and salt bridge dynamics. Similarly, in nucleic acid systems, the tool distinguished differential binding mechanisms between ochratoxin A and norfloxacin by revealing unique interaction patterns at critical nucleobases correlating with binding affinities. The tool has been validated through the analysis of over 150 simulation trajectories, covering 40,000 ns of total simulation time and 20 systems. gmx_RRCS significantly advances structural/molecular biology studies by enhancing our understanding of protein conformational dynamics, thereby facilitating rational drug design. gmx_RRCS is freely available on GitHub (https://github.com/RuijinHospitalRCMSB/gmx_RRCS) and PyPI (https://pypi.org/project/gmx-RRCS).</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169129"},"PeriodicalIF":4.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794437","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

DeepAssembly2: A Web Server for Protein Complex Structure Assembly Based on Domain-Domain Interactions. 基于域-域交互的蛋白质复杂结构组装Web服务器DeepAssembly2。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2025-04-04 DOI: 10.1016/j.jmb.2025.169128

Yuhao Xia, Yilin Pu, Suhui Wang, Jianan Zhuang, Dong Liu, Minghua Hou, Guijun Zhang

{"title":"DeepAssembly2: A Web Server for Protein Complex Structure Assembly Based on Domain-Domain Interactions.","authors":"Yuhao Xia, Yilin Pu, Suhui Wang, Jianan Zhuang, Dong Liu, Minghua Hou, Guijun Zhang","doi":"10.1016/j.jmb.2025.169128","DOIUrl":"https://doi.org/10.1016/j.jmb.2025.169128","url":null,"abstract":"<p><p>Proteins often perform biological functions by forming complexes, thereby accurately predicting the structure of protein complexes is crucial to understanding and mastering their functions, as well as facilitating drug discovery. Protein monomeric structure prediction has made a breakthrough in recent years, but the accurate prediction of complex structure remains a challenge. In this work, we present DeepAssembly2, a web server for automatically assembling protein complex structure based on domain-domain interactions. First, the features are constructed according to the input complex sequence and monomeric structures, then these features are used to predict the inter-chain residue distance through a deep learning model, and finally, the complex structure is assembled under the guidance of inter-chain residue distances. Compared with the previously developed version, DeepAssembly2 is trained on a newly constructed inter-chain domain-domain interaction dataset. Meanwhile, several important features have been added, such as Interface Residue Propensity and Ultrafast Shape Recognition. In addition, we introduced the inter-chain residue distance from the AlphaFold-Multimer model to further improve the accuracy. Finally, we also integrate our recently developed model quality assessment method to select the output models. The performance of DeepAssembly2 is significantly improved compared with the previous version, and it is expected to provide new insights and an effective tool for drug development, vaccine design, etc. The web server of DeepAssembly2 is freely available at http://zhanglab-bioinf.com/DeepAssembly/.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169128"},"PeriodicalIF":4.7,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794486","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