Journal of Molecular Biology最新文献_第3页

Microglial ITAM & ITIM Signaling in Neurodegenerative Disease and Brain Aging. 小胶质ITAM和ITIM信号在神经退行性疾病和脑老化中的作用。

IF 4.7 2区生物学

Journal of Molecular Biology Pub Date : 2026-06-10 DOI: 10.1016/j.jmb.2026.169910

Aman Mangalmurti, Amelia Bonheur, John R Lukens

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":"<p><p>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.</p>","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 Anticancer Drug Mitoxantrone Triggers the Formation of Ribosome-enriched Stress Granules Independently of the Classical Translational Control Pathways 抗癌药物米托蒽醌触发核糖体富集应激颗粒的形成，独立于经典的翻译控制途径。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-01 Epub Date: 2026-02-02 DOI: 10.1016/j.jmb.2026.169671

Marta Leśniczak-Staszak , Paulina Pietras , Agnieszka Fedoruk-Wyszomirska , Martino Morici , Mateusz Sowiński , Szymon Krawczyk , Małgorzata Andrzejewska , Eliza Wyszko , Michał Nowicki , Paul J. Anderson , Ewelina Gowin , Pavel Ivanov , Daniel N. Wilson , Witold Szaflarski

{"title":"The Anticancer Drug Mitoxantrone Triggers the Formation of Ribosome-enriched Stress Granules Independently of the Classical Translational Control Pathways","authors":"Marta Leśniczak-Staszak , Paulina Pietras , Agnieszka Fedoruk-Wyszomirska , Martino Morici , Mateusz Sowiński , Szymon Krawczyk , Małgorzata Andrzejewska , Eliza Wyszko , Michał Nowicki , Paul J. Anderson , Ewelina Gowin , Pavel Ivanov , Daniel N. Wilson , Witold Szaflarski","doi":"10.1016/j.jmb.2026.169671","DOIUrl":"10.1016/j.jmb.2026.169671","url":null,"abstract":"<div><div>Mitoxantrone (MIT) is a chemotherapeutic drug widely used for its DNA intercalation and inhibition of topoisomerase. In this work, we show that MIT also affects cytoplasmic RNA–ribosome organization. In human cancer cells, MIT induced stress granules (SGs) that contained large ribosomal subunit proteins, including eL8, together with polyadenylated mRNA. These MIT-induced SGs were different from arsenite-induced SGs: they formed without eIF2α phosphorylation, mTOR inhibition, or 4E-BP1 activity, and they remained stable in the presence of cycloheximide and after drug withdrawal. In vitro assays further demonstrated that MIT promotes ribosome aggregation in a concentration- and salt-dependent manner. Taken together, our results identify a distinct type of ribosome-enriched SGs that form through RNA–ribosome condensation rather than classical translational stress pathways. This mechanism provides a direct example of how a clinically used drug can reorganize cytoplasmic RNA–protein complexes, with possible consequences for mRNA regulation, cancer therapy, and neurodegenerative disease.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"438 7","pages":"Article 169671"},"PeriodicalIF":4.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117274","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

Rising Stars: Adaptation to Environment: From Hormone Signaling to Gene Silencing 冉冉升起的新星：适应环境：从激素信号到基因沉默。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-01 Epub Date: 2026-01-29 DOI: 10.1016/j.jmb.2026.169665

Hongwei Guo, Yichuan Wang, Zhenyu Wang, Yuelin Liu

{"title":"Rising Stars: Adaptation to Environment: From Hormone Signaling to Gene Silencing","authors":"Hongwei Guo, Yichuan Wang, Zhenyu Wang, Yuelin Liu","doi":"10.1016/j.jmb.2026.169665","DOIUrl":"10.1016/j.jmb.2026.169665","url":null,"abstract":"<div><div>The survival of plants depends on sensitive and efficient systems that perceive and integrate internal hormonal signals with external environmental cues. Deciphering how plants sense and adapt to changing conditions is a fundamental biological question with direct relevance to crop improvement and sustainable agriculture. Hongwei Guo received training in plant molecular genetics and light signaling during his doctoral studies, then turned to how diverse signal pathways converge to coordinate plant development. In his postdoctoral work, he identified EBF1/2-mediated ubiquitin–proteasome turnover of EIN3 as a core mechanism of ethylene signaling. Building on this foundation, his independent research uncovered additional post-transcriptional strategies: proteolytic cleavage and translational repression that fine-tune ethylene responses. He also established an EIN3-centered regulatory network that integrates hormonal and environmental cues to coordinate diverse physiological processes. A forward genetic screen of ethylene-activated plants unexpectedly extended Dr. Guo’s research to siRNA-based regulation. His group discovered a cytoplasmic “dual-safeguard” mechanism in which impairment of mRNA decay triggers the production of coding-transcript–derived siRNAs (ct-siRNAs) that silence endogenous genes. They further showed that stress-induced 22-nt ct-siRNAs amplify silencing to modulate nitrate assimilation and energy balance under abiotic stress. More recently, Dr. Guo’s laboratory has focused on how plant cells sense physical and chemical changes in their surroundings. They identified two extracellular peptide–receptor complexes as apoplastic pH sensors, and demonstrated that cytoplasmic protein DCP5 senses osmotic stress through phase separation to form new stress granules and rapidly reprogram gene expression. Collectively, Dr. Guo’s research connects hormone signaling, gene regulation, and environmental adaptation.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"438 7","pages":"Article 169665"},"PeriodicalIF":4.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096690","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 Basis for Non-classical WIN Peptides Recognition by WDR5 WDR5识别非经典WIN多肽的结构基础。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-01 Epub Date: 2026-01-30 DOI: 10.1016/j.jmb.2026.169666

Yang Yang , Yan Pan , Qingying Wang , Hao Li , Shuting Zhang , Xuefang Sun , Lingyun Xia , Li Xu , Xuemin Chen

{"title":"Structural Basis for Non-classical WIN Peptides Recognition by WDR5","authors":"Yang Yang , Yan Pan , Qingying Wang , Hao Li , Shuting Zhang , Xuefang Sun , Lingyun Xia , Li Xu , Xuemin Chen","doi":"10.1016/j.jmb.2026.169666","DOIUrl":"10.1016/j.jmb.2026.169666","url":null,"abstract":"<div><div>WD repeat–containing protein 5 (WDR5) is a core scaffolding component of multiple chromatin-modifying complexes that engages diverse partner proteins through a conserved arginine-binding cavity known as the WDR5-interacting (WIN) site. Dysregulation of WDR5 has been implicated in oncogenesis, making the WIN site a promising therapeutic target. Current inhibitor development has primarily focused on mimicking canonical WIN motif interactions, thereby limiting exploration of alternative recognition modes. Here, we present high-resolution crystal structures of two arginine-containing peptide probes that reveal previously unrecognized binding geometries at the WIN pocket. One peptide adopts an extended linear conformation that bridges both the WIN pocket and the adjacent S7 site. The other binds in a reversed, or “<em>trans</em>-WIN,” orientation, in which a C-terminal arginine anchors the WIN site while an upstream proline residue occupies the S7 pocket. Isothermal titration calorimetry confirmed moderate and specific affinities for both peptides. These findings reveal unexpected conformational adaptability of the WIN site and demonstrate that its recognition capacity extends beyond the canonical mode defined by histone H3 and other partner proteins. Collectively, our results expand the structural repertoire of WIN-site recognition and establish a framework for rational design of next-generation WDR5 inhibitors that exploit multi-site engagement and alternative binding topologies.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"438 7","pages":"Article 169666"},"PeriodicalIF":4.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099548","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

Rising Star: Combining Bioinformatics and Experimental Biology to Decoding Non-coding RNAs and RNA Modifications 新星：结合生物信息学和实验生物学解码非编码RNA和RNA修饰。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-01 Epub Date: 2026-02-09 DOI: 10.1016/j.jmb.2026.169684

Xiu-Jie Wang

引用次数: 0

Oligomerization-Dependent Regulation of LrhA Controls Bacterial Flagellar Biosynthesis 寡聚化依赖性调控LrhA控制细菌鞭毛生物合成。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-01 Epub Date: 2026-02-06 DOI: 10.1016/j.jmb.2026.169682

Baichun Niu, Masahide Kikkawa, Xuguang Jiang

{"title":"Oligomerization-Dependent Regulation of LrhA Controls Bacterial Flagellar Biosynthesis","authors":"Baichun Niu, Masahide Kikkawa, Xuguang Jiang","doi":"10.1016/j.jmb.2026.169682","DOIUrl":"10.1016/j.jmb.2026.169682","url":null,"abstract":"<div><div>LysR-type transcriptional regulators (LTTRs) are a diverse family of proteins that regulate various cellular processes, including motility in bacteria. In <em>Escherichia coli</em>, the LTTR LrhA represses flagellar biosynthesis by inhibiting the <em>flhDC</em> operon. However, the structural basis underlying this regulation has remained unclear. Here, we determined both a high-resolution crystal structure and a cryo-EM reconstruction of LrhA, revealing a predominant and stable tetrameric organization with pronounced structural variability in its effector-binding region. Structural and biochemical analyses demonstrate that mutations in these variable regions perturb the oligomeric equilibrium of LrhA, shifting the balance between tetrameric and dimeric species. This shift correlates with enhanced DNA binding affinity and stronger repression of the <em>flhDC</em> promoter. While ligand binding may similarly modulate LrhA activity, our data primarily support a model in which alterations in oligomeric state mediated by the variable regions regulate LrhA function. Together, these findings provide a structural framework for understanding how LrhA controls bacterial motility and offer broader insights into oligomerization-based regulation within the LTTR family.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"438 7","pages":"Article 169682"},"PeriodicalIF":4.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140736","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

Rising Stars: Molecular Mechanisms of Ligand Recognition and Functional Modulation of GPCRs 新兴之星：gpcr配体识别和功能调节的分子机制。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-01 Epub Date: 2026-02-05 DOI: 10.1016/j.jmb.2026.169674

Shuo Han , Qiuxiang Tan , Shuling Lin , Kun Chen , Maozhou He , Qiang Zhao , Beili Wu

{"title":"Rising Stars: Molecular Mechanisms of Ligand Recognition and Functional Modulation of GPCRs","authors":"Shuo Han , Qiuxiang Tan , Shuling Lin , Kun Chen , Maozhou He , Qiang Zhao , Beili Wu","doi":"10.1016/j.jmb.2026.169674","DOIUrl":"10.1016/j.jmb.2026.169674","url":null,"abstract":"<div><div>In response to a variety of signals outside of cells, G protein-coupled receptors (GPCRs) play essential roles in cell signal transduction by relaying the extracellular signals to the intracellular side through various signaling mechanisms, which govern diverse physiological and pathological processes. These receptors are involved in many diseases and comprise the largest drug target family. However, the molecular mechanisms underlying the GPCR signal transduction are poorly understood, which hinders the drug discovery with only a small portion of receptors having drugs marketed. Over the past decade, our laboratory has been focused on the ligand recognition and functional modulation mechanisms of different GPCRs, aiming for better understanding of the physiology and pathology of this receptor superfamily and new clues to carry out drug development. Through extensive structural and functional studies, we uncovered diverse interaction patterns of GPCRs in recognizing various ligands, including small molecules, peptides, and proteins. These molecular details not only reveal key factors that define ligand selectivity and receptor specificity, but also provide insights into allosteric modulation, ligand promiscuity, and intrinsic activation. Our knowledge about the GPCR modulations were further extended by investigating the conformational rearrangements and dynamics of GPCRs upon activation and coupling to downstream signaling transducers. With different molecular architectures, different receptors exhibit distinct patterns in regulating their activities and abilities to stimulate various signaling pathways, which are key for understanding biased signaling. These findings demonstrate the diversity and complexity of GPCR signaling and would enable development of novel drugs with improved efficacy and reduced side effects.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"438 7","pages":"Article 169674"},"PeriodicalIF":4.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130784","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

Rising Stars: In vivo Monitoring of Neurochemical Dynamics by Genetically Encoded Neuromodulator Sensors 后起之秀：通过基因编码的神经调节传感器在体内监测神经化学动力学。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-01 Epub Date: 2026-01-30 DOI: 10.1016/j.jmb.2026.169669

Shengwei Fu , Yulong Li

引用次数: 0

Rising Star: Single Cell Omics Technologies: When Whole Omics Analysis Meets Single Cell Resolution 新星：单细胞组学技术：当全组学分析满足单细胞分辨率时。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-04-01 Epub Date: 2026-01-30 DOI: 10.1016/j.jmb.2026.169670

Fuchou Tang

{"title":"Rising Star: Single Cell Omics Technologies: When Whole Omics Analysis Meets Single Cell Resolution","authors":"Fuchou Tang","doi":"10.1016/j.jmb.2026.169670","DOIUrl":"10.1016/j.jmb.2026.169670","url":null,"abstract":"<div><div>I got my PhD degree under the supervision of Prof. Kegang Shang in 2003. And I did my postdoc research in Azim Surani’s lab. Then I set up my own lab in Biomedical Pioneering Innovation Center at Peking University in 2010. My research has focused on developing single-cell omics sequencing technologies and employing these powerful tools to dissect the gene regulation networks in human germline cell development under both physiological and pathological conditions. My lab systematically developed a serial of single-cell omics sequencing technologies, including the first single-cell DNA methylome sequencing technology in 2013, which was considered to pioneer the single-cell epigenome field. In recent years, my lab has focused on developing single-cell omics long-read sequencing technologies based on single-molecule sequencing platforms, which can reveal critical features of the repetitive elements. The repetitive elements are considered as ‘dark matter’, which account for over half of our genome and play important roles for both normal development and numerous diseases. The research in my lab revealed critical features of the epigenetic reprogramming of human germline cells, deepening our understanding of these cells, which are fundamental to the transgenerational immortality of the human species.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"438 7","pages":"Article 169670"},"PeriodicalIF":4.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099733","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