Journal of Molecular Biology最新文献

Molecular Determinants of Response and Rational Drug Combinations for Antibody-Drug Conjugates (ADCs) with Topoisomerase I (TOP1) Inhibitor payloads. 具有拓扑异构酶I （TOP1）抑制剂有效载荷的抗体-药物偶联物（adc）反应和合理药物组合的分子决定因素。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-05-04 DOI: 10.1016/j.jmb.2026.169841

Yves Pommier

引用次数: 0

MoonProt 4.0: 2026 Update of the Moonlighting Proteins Database. MoonProt 4.0: 2026月光蛋白数据库的更新。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-30 DOI: 10.1016/j.jmb.2026.169840

Aini Asif, Nour Farache, Wael Farache, Amman Hossain, Pranav Harish, Constance Jeffery

引用次数: 0

Multifaceted Roles of the NLRC4 Inflammasome in Cancer: From Molecular Mechanisms to Therapeutic Implications. NLRC4炎症小体在癌症中的多面作用：从分子机制到治疗意义

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-28 DOI: 10.1016/j.jmb.2026.169829

Zhen Zhang, Yang Li, Zhimeng Lv, Si Ming Man

{"title":"Multifaceted Roles of the NLRC4 Inflammasome in Cancer: From Molecular Mechanisms to Therapeutic Implications.","authors":"Zhen Zhang, Yang Li, Zhimeng Lv, Si Ming Man","doi":"10.1016/j.jmb.2026.169829","DOIUrl":"10.1016/j.jmb.2026.169829","url":null,"abstract":"NLRC4 forms an inflammasome complex and activates a critical innate immune response to bacterial infection. The NLRC4 inflammasome triggers the activation of the cysteine protease caspase-1, leading to the proteolytic maturation of the pro-inflammatory cytokines IL-1β and IL-18, and the induction of pyroptosis. The role of NLRC4 in antimicrobial defense is well-established, but emerging evidence highlights a complex and often paradoxical functions of NLRC4 in the development and progression of cancer. NLRC4 acts as a tumor suppressor in colorectal and intestinal cancer, and potentially melanoma. NLRC4 also forms unique tumor-attenuating protein complexes, independently of NAIPs, ASC and caspase-1, that activate the DNA damage response. In obesity-associated cancers and metastasis, NLRC4 is pro-tumorigenic and promotes pathological inflammation and angiogenesis. Understanding the precise regulatory mechanisms of NLRC4 in cancer will provide insights into the development of personalized immunotherapies. This review discusses the multi-functional roles of NLRC4 in cancer and explores the potential clinical utility of targeting NLRC4 in therapies.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169829"},"PeriodicalIF":4.5,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809498","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

The role of nonsense-mediated mRNA decay in aging. 无义介导的mRNA衰变在衰老中的作用。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-28 DOI: 10.1016/j.jmb.2026.169830

Eunseok Kang, Hyunwoo C Kwon, Seung-Jae V Lee

引用次数: 0

Translatable Circular RNAs are Degraded Via Nonsense-mediated mRNA Decay. 可翻译的环状rna通过无义介导的mRNA衰变而降解。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-26 DOI: 10.1016/j.jmb.2026.169828

Eunchae Kang, Dahyeon Kang, Yeo Kyung Cho, Min-Kyung Shin, Sung Ho Boo, Jeeyoon Chang, Hyeong-In Kim, Jae Hee Jo, Yoon Ki Kim

{"title":"Translatable Circular RNAs are Degraded Via Nonsense-mediated mRNA Decay.","authors":"Eunchae Kang, Dahyeon Kang, Yeo Kyung Cho, Min-Kyung Shin, Sung Ho Boo, Jeeyoon Chang, Hyeong-In Kim, Jae Hee Jo, Yoon Ki Kim","doi":"10.1016/j.jmb.2026.169828","DOIUrl":"10.1016/j.jmb.2026.169828","url":null,"abstract":"Endogenous circular RNAs (circRNAs) are predominantly generated by a back-splicing process. Due to their lacking 5' and 3' termini, circRNA degradation is exclusively dependent on endoribonucleolytic cleavage. In addition, translation occurring on circRNAs depends solely on internal ribosome entry site (IRES) or IRES-like features, such as an exon junction complex (EJC) deposited after back-splicing. However, the potential relationship between the translatability and stability of circRNAs has yet to be explored. Here, we demonstrate that translatable circRNAs can be subject to canonical EJC-dependent nonsense-mediated mRNA decay (NMD), a well-known mRNA surveillance mechanism, as long as circRNAs contain EJC(s) downstream of a translation termination codon. We find that the NMD of translatable circRNAs involves UPF1 and the NMD-specific endoribonuclease SMG6. This distinct pathway is termed NMD-like circRNA decay (NCD). The differences in factor requirements between canonical EJC-dependent NMD and NCD lead to variations in RNA regulation under cellular stress conditions. Our observations provide an additional layer in the molecular regulation of circRNA dynamics.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169828"},"PeriodicalIF":4.5,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759022","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

Structural Insights into Tanc1/2 Autoinhibition and Their Implications for NDD Pathogenesis. tan1 /2自抑制的结构见解及其对NDD发病机制的影响。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-24 DOI: 10.1016/j.jmb.2026.169827

Dengqin Zhong, Chenyang Xue, Mengjie Lyu, Dongsheng Zhang, Qiangou Chen, Jun Li, Yanan Wang, An Liu, Wei Xie, Yongping Cui, Kang Xiao, Zhongmin Liu, Wei Liu

{"title":"Structural Insights into Tanc1/2 Autoinhibition and Their Implications for NDD Pathogenesis.","authors":"Dengqin Zhong, Chenyang Xue, Mengjie Lyu, Dongsheng Zhang, Qiangou Chen, Jun Li, Yanan Wang, An Liu, Wei Xie, Yongping Cui, Kang Xiao, Zhongmin Liu, Wei Liu","doi":"10.1016/j.jmb.2026.169827","DOIUrl":"10.1016/j.jmb.2026.169827","url":null,"abstract":"Tanc1 and Tanc2 are synaptic scaffold proteins with high structural similarity but distinct expression patterns and functions. Although accumulating evidence points to important divergent roles of Tanc1 and Tanc2 in neural development, the precise molecular mechanisms governing their activity (e.g., autoinhibition and activation) and their pathogenic pathways in neurodevelopmental disorders remain poorly defined. Here, we investigated the molecular basis underlying mouse Tanc1 and Tanc2 autoinhibition, ATP-dependent activation, and disease-mutation induced hyperactivation. Using cryogenic electron microscopy (cryo-EM), we determined the monomeric structures of mouse Tanc1 (215-1452) and Tanc2 (211-1421) in their monomeric states and identified them as STAND/NACHT ATPases, thereby further extend the functional implications of the STAND/NACHT family in neurodevelopmental disorders. And we further revealed their distinct autoinhibitory mechanisms: mTanc1 adopts a closed, inactive conformation stabilized by a 226-231 \"lock\" segment, whereas mTanc2 dynamically switches between closed and pre-activated states to enable ATP-dependent oligomerization. Biochemical and cellular assays further demonstrated that mTanc2 forms active oligomers with strong ATPase activity and cytoplasmic puncta formation. Notably, neurodevelopmental disorder-associated mTanc2 mutations (R755H, A794V, C890R) further enhanced oligomerization, elevated ATPase activity, and triggered apoptosis, pointing to a hyperactivation-driven pathogenic mechanism. Collectively, these findings reveal distinct autoinhibitory mechanisms within the Tanc family, explain mTanc2's activation propensity, and link its hyperactivation to neuronal dysfunction and neurodevelopmental disorder pathology.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169827"},"PeriodicalIF":4.5,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759035","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

Identification of non-basic matrix domain residues that impact HTLV-1 Gag membrane targeting and particle release. 影响HTLV-1 Gag膜靶向和颗粒释放的非碱性基质结构域残基的鉴定。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-22 DOI: 10.1016/j.jmb.2026.169826

Shuyu Meng, Bao Pham, Sophie Hines, Isaac Angert, Dalton W Piotter, Joachim D Mueller, Jamil S Saad, Wei Zhang, Louis M Mansky

{"title":"Identification of non-basic matrix domain residues that impact HTLV-1 Gag membrane targeting and particle release.","authors":"Shuyu Meng, Bao Pham, Sophie Hines, Isaac Angert, Dalton W Piotter, Joachim D Mueller, Jamil S Saad, Wei Zhang, Louis M Mansky","doi":"10.1016/j.jmb.2026.169826","DOIUrl":"https://doi.org/10.1016/j.jmb.2026.169826","url":null,"abstract":"The matrix (MA) domain of the Gag polyprotein is critical for directing retroviral assembly at the plasma membrane (PM), yet the determinants mediating human T-cell leukemia virus type 1 (HTLV-1) Gag targeting remain incompletely defined. While Gag myristoylation and basic residue-mediated electrostatic interactions are known to be crucial for Gag-PM interactions, recent evidence with HTLV-1 MA has implicated limited dependency on specific lipid headgroup recognition for the ability of Gag to interact with the PM. Here, we have analyzed the role of non-basic residues in HTLV-1 MA in membrane interactions and particle assembly. We identified several residues (i.e., L19, D42, S70, and L71) that were essential for Gag targeting to the PM, where mutation of these amino acid residues led to Gag targeting to internal locations that colocalized with late endosomal markers. Mutation of L19 and D42 was found to alter the MA structure. Taken together, these data indicate that mutation of MA non-basic amino acid residues allowed for particle production and also led to Gag localization to internal membranes that colocalized with late endosome markers. These observations indicate that non-basic residues play an important role in efficient particle assembly and release of HTLV-1 from cells.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169826"},"PeriodicalIF":4.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758980","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

Molecular dissection of the UvrC protein involved in nucleotide excision repair in Listeria monocytogenes. 单核增生李斯特菌核苷酸切除修复中UvrC蛋白的分子解剖。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-22 DOI: 10.1016/j.jmb.2026.169825

Preetha C Sivadasan, Manoj Thakur, K Neelakanteshwar Patil

{"title":"Molecular dissection of the UvrC protein involved in nucleotide excision repair in Listeria monocytogenes.","authors":"Preetha C Sivadasan, Manoj Thakur, K Neelakanteshwar Patil","doi":"10.1016/j.jmb.2026.169825","DOIUrl":"https://doi.org/10.1016/j.jmb.2026.169825","url":null,"abstract":"Nucleotide excision repair (NER) is a conserved DNA repair pathway that removes a wide range of DNA lesions and preserves genome integrity. In bacteria, this process is executed by the UvrABC excinuclease complex, in which UvrC performs dual incisions flanking damaged sites. Despite its central role in repair, the biochemical properties and mechanistic features of UvrC from several pathogenic bacteria remain poorly defined. Here, we present a biochemical characterization of UvrC from Listeria monocytogenes (LmUvrC), a major food-borne pathogen. LmUvrC exhibits robust DNA-binding capability and DNA incision activity. Size-exclusion chromatography analyses reveal that LmUvrC predominantly exists as a monomer in solution. We further identify a cysteine-rich region capable of coordinating an iron-sulfur cluster, whose deletion results in a pronounced loss of DNA-binding ability. Systematic deletion of various domains demonstrates that efficient incision by LmUvrC relies on coordinated contributions from both the GIY-YIG and RNase H domains, highlighting the importance of interdomain synergy and UvrB-mediated activation. Together, these findings establish a biochemical framework for UvrC, providing insights into NER in L. monocytogenes and highlight new mechanistic features of bacterial NER.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169825"},"PeriodicalIF":4.5,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759032","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

LinkCraft: An interactive tool for the design of flexible linkers. LinkCraft：一个设计柔性连接器的交互式工具。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-17 DOI: 10.1016/j.jmb.2026.169814

Mátyás Pajkos, Pierre Barrera, Ilinka Clerc, Christophe Zanon, Pau Bernadó, Juan Cortés

{"title":"LinkCraft: An interactive tool for the design of flexible linkers.","authors":"Mátyás Pajkos, Pierre Barrera, Ilinka Clerc, Christophe Zanon, Pau Bernadó, Juan Cortés","doi":"10.1016/j.jmb.2026.169814","DOIUrl":"10.1016/j.jmb.2026.169814","url":null,"abstract":"Multi-domain proteins connect functional domains through flexible linkers that critically determine their spatial arrangement and cooperative behavior. Most inter-domain linkers are intrinsically disordered regions (IDRs), whose conformational flexibility is essential for function. The design of such multimodular proteins is becoming increasingly important in biotechnology and synthetic biology, where engineered assemblies combine catalytic, regulatory, or binding domains to create systems with desired functionalities. However, although domain engineering is now well established, rational linker design remains challenging because linker properties depend on multiple coupled factors, including sequence composition, charge patterning, and length. Here, we present LinkCraft, a computational tool for the rational design of intrinsically disordered linkers (IDLs) in multi-domain proteins. LinkCraft suggests a range of suitable IDL lengths as a function of the inter-domain distance and supports custom linker sequence definition or sequence generation based on desired physicochemical properties. The ensemble-based modeling of the designed multi-modular protein enables users to evaluate linker behavior and dynamics within its structural context. The tool provides an easy-to-use framework for prototyping complex protein constructions, promoting a shift from domain-centric to multi-modular-centric protein design, where linkers are treated as active, tunable determinants of molecular function. LinkCraft is freely available at https://gitlab.laas.fr/moma/binaries/linkcraft/.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169814"},"PeriodicalIF":4.5,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721412","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

Deeptosis: A Deep Learning-Based Platform for Label-Free Discrimination of Apoptosis and Pyroptosis from Brightfield Microscopy. Deeptosis：一个基于深度学习的平台，用于明视野显微镜下细胞凋亡和焦亡的无标记区分。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-16 DOI: 10.1016/j.jmb.2026.169815

Haiji Wang, Shaofeng Lin, Chenbei Li, Fengzi Zhang, Yuyuan Zhu, Xu Liu, Cainian Huang, Min Cao, Sijia Jiang, Yaqin Liu, Tao Wang, Lijie Wang, Shuaijie Liu, Haodong Xu, Liming Wang

{"title":"Deeptosis: A Deep Learning-Based Platform for Label-Free Discrimination of Apoptosis and Pyroptosis from Brightfield Microscopy.","authors":"Haiji Wang, Shaofeng Lin, Chenbei Li, Fengzi Zhang, Yuyuan Zhu, Xu Liu, Cainian Huang, Min Cao, Sijia Jiang, Yaqin Liu, Tao Wang, Lijie Wang, Shuaijie Liu, Haodong Xu, Liming Wang","doi":"10.1016/j.jmb.2026.169815","DOIUrl":"10.1016/j.jmb.2026.169815","url":null,"abstract":"Motivation: Accurately distinguishing apoptosis from pyroptosis is essential for studying regulated cell death and its roles in immunity and disease, but their similar morphologies and shared upstream signals make label-free bright-field discrimination difficult.Results: We present Deeptosis, an end-to-end deep learning pipeline that performs automatic cell segmentation (Cellpose) and single-cell classification with a Vision Transformer (ViT). Trained on 26,565 manually annotated bright-field cells (apoptosis, pyroptosis, other), the model achieved a mean AUROC of 0.999 in five-fold cross-validation and retained high performance on an independent test set (AUROC 0.990 apoptosis, 0.982 pyroptosis, 0.983 other). The system outputs color-coded visualization and a per-cell CSV containing coordinates, labels, and confidence scores, and can be operated through a web interface for batch analysis.Availability: Source code and scripts are available at GitHub (https://github.com/Bamba-WangLab/Deeptosis); a prototype web app (http://modinfor.com/Deeptosis) demonstrates the workflow.Conclusion: Deeptosis provides a label-free framework for quantitative analysis of cell death modalities.","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169815"},"PeriodicalIF":4.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715422","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