Structure最新文献_第8页

Deciphering the molecular mechanism underlying morphology transition in two-component DNA-protein cophase separation 破译双组分 DNA 蛋白共相分离中形态转变的分子机制

IF 5.7 2区生物学

Structure Pub Date : 2024-11-13 DOI: 10.1016/j.str.2024.10.026

Cheng Li, Yunqiang Bian, Yiting Tang, Lingyu Meng, Peipei Yin, Ye Hong, Jun Cheng, Yuchen Li, Jie Lin, Chao Tang, Chunlai Chen, Wenfei Li, Zhi Qi

{"title":"Deciphering the molecular mechanism underlying morphology transition in two-component DNA-protein cophase separation","authors":"Cheng Li, Yunqiang Bian, Yiting Tang, Lingyu Meng, Peipei Yin, Ye Hong, Jun Cheng, Yuchen Li, Jie Lin, Chao Tang, Chunlai Chen, Wenfei Li, Zhi Qi","doi":"10.1016/j.str.2024.10.026","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.026","url":null,"abstract":"Nucleic acid and protein co-condensates exhibit diverse morphologies crucial for fundamental cellular processes. Despite many previous studies that advanced our understanding of this topic, several interesting biophysical questions regarding the underlying molecular mechanisms remain. We investigated DNA and human transcription factor p53 co-condensates—a scenario where neither dsDNA nor the protein demonstrates phase-separation behavior individually. Through a combination of experimental assays and theoretical approaches, we elucidated: (1) the phase diagram of DNA-protein co-condensates at a certain observation time, identifying a phase transition between viscoelastic fluid and viscoelastic solid states, and a morphology transition from droplet-like to “pearl chain”-like co-condensates; (2) the growth dynamics of co-condensates. Droplet-like and “pearl chain”-like co-condensates share a common initial critical microscopic cluster size at the nanometer scale during the early stage of phase separation. These findings provide important insights into the biophysical mechanisms underlying multi-component phase separation within cellular environments.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"216 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601001","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

Mechanism of negative μ-opioid receptor modulation by sodium ions 钠离子调节负μ-阿片受体的机制

IF 5.7 2区生物学

Structure Pub Date : 2024-11-12 DOI: 10.1016/j.str.2024.10.023

Neil J. Thomson, Ulrich Zachariae

引用次数: 0

Targeting adhesion G protein-coupled receptors. Current status and future perspectives 靶向粘附 G 蛋白偶联受体。现状与未来展望

IF 5.7 2区生物学

Structure Pub Date : 2024-11-08 DOI: 10.1016/j.str.2024.10.022

Fabian Liessmann, Lukas von Bredow, Jens Meiler, Ines Liebscher

{"title":"Targeting adhesion G protein-coupled receptors. Current status and future perspectives","authors":"Fabian Liessmann, Lukas von Bredow, Jens Meiler, Ines Liebscher","doi":"10.1016/j.str.2024.10.022","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.022","url":null,"abstract":"G protein-coupled receptors (GPCRs) orchestrate many physiological functions and are a crucial target in drug discovery. Adhesion GPCRs (aGPCRs), the second largest family within this superfamily, are promising yet underexplored targets for treating various diseases, including obesity, psychiatric disorders, and cancer. However, the receptors’ unique and complex structure and miscellaneous interactions complicate comprehensive pharmacological studies. Despite recent progress in determining structures and elucidation of the activation mechanism, the function of many receptors remains to be determined.This review consolidates current knowledge on aGPCR ligands, focusing on small molecule orthosteric ligands and allosteric modulators identified for the ADGRGs subfamily (subfamily VIII), (GPR56/ADGRG1, GPR64/ADGRG2, GPR97/ADGRG3, GPR114/ADGRG5, GPR126/ADGRG6, and GPR128/ADGRG7). We discuss challenges in hit identification, target validation, and drug discovery, highlighting molecular compositions and recent structural breakthroughs. ADGRG ligands can offer new insights into aGPCR modulation and have significant potential for novel therapeutic interventions targeting various diseases.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"145 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596474","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

Ringing the changes: Regulation of Parkin activity by different ubiquitin and ubiquitin-like proteins 环形变化：不同泛素和泛素样蛋白对 Parkin 活性的调控

IF 5.7 2区生物学

Structure Pub Date : 2024-11-07 DOI: 10.1016/j.str.2024.10.015

Shalini Iyer, Chittaranjan Das

引用次数: 0

Multi-step shapeshifting of SARS-CoV-2 Omicron spikes during fusion SARS-CoV-2 Omicron 穗状病毒在融合过程中的多步变形

IF 5.7 2区生物学

Structure Pub Date : 2024-11-07 DOI: 10.1016/j.str.2024.10.017

Wang Xu, Yang Han, Maolin Lu

引用次数: 0

Traces of convergent evolution left in the structure of EgtB-IV EgtB-IV 结构中留下的趋同进化痕迹

IF 5.7 2区生物学

Structure Pub Date : 2024-11-07 DOI: 10.1016/j.str.2024.10.006

Taku Mizutani, Ikuro Abe

引用次数: 0

Visualizing the dual interaction of calcineurin with PI4KA and FAM126A 钙调素与 PI4KA 和 FAM126A 的双重相互作用的可视化

IF 5.7 2区生物学

Structure Pub Date : 2024-11-07 DOI: 10.1016/j.str.2024.10.010

Qingtong Zhou, Xiao Liu, Ming-Wei Wang

引用次数: 0

Structure, function, surf, repeat: A week at Lorne Proteins 2024 结构、功能、冲浪、重复：2024 年洛恩蛋白质展一周回顾

IF 5.7 2区生物学

Structure Pub Date : 2024-11-07 DOI: 10.1016/j.str.2024.10.007

Rosemary J. Cater, Renae M. Ryan, Jonathan S. Oakhill, Peter Czabotar, James M. Murphy, Melissa J. Call

引用次数: 0

IspE kinase as an anti-infective target: Role of a hydrophobic pocket in inhibitor binding 作为抗感染靶标的 IspE 激酶：疏水袋在抑制剂结合中的作用

IF 5.7 2区生物学

Structure Pub Date : 2024-11-06 DOI: 10.1016/j.str.2024.10.009

Rawia Hamid, Danica J. Walsh, Eleonora Diamanti, Diana Aguilar, Antoine Lacour, Mostafa M. Hamed, Anna K.H. Hirsch

引用次数: 0

AI-driven mechanistic analysis of conformational dynamics in CNNM/CorC Mg2+ transporters 人工智能驱动的 CNNM/CorC Mg2+ 转运体构象动力学机理分析

IF 5.7 2区生物学

Structure Pub Date : 2024-11-06 DOI: 10.1016/j.str.2024.10.021

Jie Ma, Xingyu Song, Yosuke Funato, Xinyu Teng, Yichen Huang, Hiroaki Miki, Wenning Wang, Motoyuki Hattori

{"title":"AI-driven mechanistic analysis of conformational dynamics in CNNM/CorC Mg2+ transporters","authors":"Jie Ma, Xingyu Song, Yosuke Funato, Xinyu Teng, Yichen Huang, Hiroaki Miki, Wenning Wang, Motoyuki Hattori","doi":"10.1016/j.str.2024.10.021","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.021","url":null,"abstract":"The CNNM/CorC Mg2+ transporters are widely conserved in eukaryotes (cyclin M [CNNM]) and prokaryotes (CorC) and participate in various biological processes. Previous structural analyses of the CorC transmembrane domain in the Mg2+-bound inward-facing conformation revealed the conserved Mg2+ recognition mechanism in the CNNM/CorC family; however, the conformational dynamics in the Mg2+ transport cycle remain unclear because structures in other conformations are unknown. Here, we used AlphaFold structure prediction to predict the occluded-like and outward-facing-like conformations of the CorC and CNNM proteins and identified conserved hydrophilic interactions close to the cytoplasmic side in these conformations. Molecular dynamics simulations and biochemical cross-linking showed that these conserved hydrophilic interactions are stable, especially in the outward-facing-like conformation. Furthermore, mutational analysis revealed that the residues involved in these hydrophilic interactions on the cytoplasmic side are important for Mg2+ transport in the CorC and CNNM proteins. Our work provides mechanistic insights into the transport cycle of the CNNM/CorC family.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"19 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142588816","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