IF 5.7 2区生物学

Structure Pub Date : 2025-04-24 DOI: 10.1016/j.str.2025.03.014

Amita Rani Sahoo, Nisha Bhattarai, Matthias Buck

{"title":"Cholesterol-dependent dimerization and conformational dynamics of EphA2 receptors from coarse-grained and all-atom simulations","authors":"Amita Rani Sahoo, Nisha Bhattarai, Matthias Buck","doi":"10.1016/j.str.2025.03.014","DOIUrl":"https://doi.org/10.1016/j.str.2025.03.014","url":null,"abstract":"The EphA2 transmembrane receptor regulates cellular growth, differentiation, and motility, and its overexpression in various cancers makes it a potential biomarker for clinical cancer management. EphA2 signaling occurs through ligand-induced dimerization where the transmembrane (TM) and juxtamembrane (JM) domains play crucial roles in stabilizing the dimer conformations, thereby facilitating signal transduction. Electrostatic interactions between basic JM residues and signaling lipids (PIP2 and PIP3) regulate phosphorylation while cholesterol’s potential role in modulating EphA2 activation remains unclear. To investigate this, we modeled the TM-full JM peptide of EphA2 and employed coarse-grain and all-atom simulations to investigate its dimerization in cholesterol-rich and cholesterol-deficient membranes. Our findings reveal that cholesterol stabilizes specific TM dimers and TM-JM interactions with PIP2, highlighting the importance of membrane composition in EphA2 dimerization, oligomerization, and clustering. These insights enhance our understanding of lipid-mediated regulation of EphA2 and its implications in receptor signaling and cancer progression.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"44 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143867002","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

Cryo-EM structures of a Xanthomonas phage: Insights into viral architecture and implications for the model phage HK97 黄单胞菌噬菌体的低温电镜结构：对病毒结构的见解和对模型噬菌体HK97的影响

IF 5.7 2区生物学

Structure Pub Date : 2025-04-23 DOI: 10.1016/j.str.2025.03.013

Mingcheng Guo, Aohan Wang, Yaqi Zheng, Chaoying Liu, Qianqian Shao, Yunfei Deng, Lin Li, Yueting Wang, Xiaofang Wang, Yue Shen, Jun Qian, Xiaofeng Zhou, Qianglin Fang

{"title":"Cryo-EM structures of a Xanthomonas phage: Insights into viral architecture and implications for the model phage HK97","authors":"Mingcheng Guo, Aohan Wang, Yaqi Zheng, Chaoying Liu, Qianqian Shao, Yunfei Deng, Lin Li, Yueting Wang, Xiaofang Wang, Yue Shen, Jun Qian, Xiaofeng Zhou, Qianglin Fang","doi":"10.1016/j.str.2025.03.013","DOIUrl":"https://doi.org/10.1016/j.str.2025.03.013","url":null,"abstract":"Xanthomonas bacteria are responsible for disease outbreaks in several hundred plant species, causing significant economic losses. Xanthomonas phages have emerged as a promising biocontrol strategy in managing various important plant diseases caused by Xanthomonas bacteria. However, structural information for Xanthomonas phages has remained limited so far. Here, we present high-resolution cryo-electron microscopy (cryo-EM) structures of the Xanthomonas citri phage ΦXacJX1 from siphoviruses. These structures include atomic models for the head, head-to-tail connector and head-proximal portion of the tail. ΦXacJX1’s head and head-to-tail connector components show significant protein sequence and structural homology with those of the model siphophage HK97. However, the in-situ structures of head-to-tail connector of phage HK97 remain unavailable. The presented structures of phage ΦXacJX1 enhance our understanding of Xanthomonas phages and the mature virion of phage HK97. They provide a valuable framework for future structural and functional studies on both Xanthomonas phages and phage HK97.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"33 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862083","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

Laminar organization of molecular complexes in a clathrin coat revealed by nanoscale protein colocalization 纳米级蛋白共定位揭示了网格蛋白外壳中分子复合物的层流组织

IF 5.7 2区生物学

Structure Pub Date : 2025-04-23 DOI: 10.1016/j.str.2025.03.012

Tai Kiuchi, Ryouhei Kobayashi, Shuichiro Ogawa, Louis L.H. Elverston, Dimitrios Vavylonis, Naoki Watanabe

{"title":"Laminar organization of molecular complexes in a clathrin coat revealed by nanoscale protein colocalization","authors":"Tai Kiuchi, Ryouhei Kobayashi, Shuichiro Ogawa, Louis L.H. Elverston, Dimitrios Vavylonis, Naoki Watanabe","doi":"10.1016/j.str.2025.03.012","DOIUrl":"https://doi.org/10.1016/j.str.2025.03.012","url":null,"abstract":"Super-resolution microscopy achieves a few nanometers resolution, but colocalization analysis in a molecular complex is limited by its labeling density. Here we present a method for quantitative mapping of molecular complexes using multiplexed super-resolution imaging, integrating exchangeable single-molecule localization (IRIS). We developed antiserum-derived Fab IRIS probes for high-density labeling of endogenous proteins and protein cluster coloring (PC-coloring), which employs pixel-based principal component analysis and clustering. PC-coloring maps regions of distinct ratios of multiple proteins, and in each region, correlation between two proteins is calculated for evaluating the complex formation. PC-coloring revealed multi-layered complex formation in a clathrin-coated structure (CCS) prior to endocytosis. Upon epidermal growth factor (EGF) stimulation, EGF receptor (EGFR)-dominant, EGFR-Grb2-complex, and Grb2-dominant regions lined up from outside the CCS rim. Along the interior of Grb2-dominant regions, CCS components (Eps15, FCHo1/2 and intersectin-1) formed a complex with Grb2 away from EGFR. The Grb2-dominant region and Grb2-CCS component complex formation probably determine EGFR recruitment sites in the CCS rim.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"108 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862085","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 structure of the R2T complex reveals a different architecture from the related HSP90 cochaperone R2TP R2T复合体的结构揭示了与相关的HSP90伴侣R2TP不同的结构

IF 5.7 2区生物学

Structure Pub Date : 2025-04-18 DOI: 10.1016/j.str.2025.04.007

Alberto Palacios-Abella, Andrés López-Perrote, Jasminka Boskovic, Sandra Fonseca, Cristina Úrbez, Vicente Rubio, Oscar Llorca, David Alabadí

引用次数: 0

Structural diversity and oligomerization of bacterial ubiquitin-like proteins 细菌泛素样蛋白的结构多样性和寡聚化

IF 5.7 2区生物学

Structure Pub Date : 2025-04-17 DOI: 10.1016/j.str.2025.03.011

Minheng Gong, Qiaozhen Ye, Yajie Gu, Lydia R. Chambers, Andrey A. Bobkov, Neal K. Arakawa, Mariusz Matyszewski, Kevin D. Corbett

引用次数: 0

High-resolution cryo-EM analysis visualizes hydrated type I and IV pilus structures from enterotoxigenic Escherichia coli 高分辨率冷冻电镜分析可视化水合型I和IV型菌毛结构从肠毒素大肠杆菌

IF 5.7 2区生物学

Structure Pub Date : 2025-04-11 DOI: 10.1016/j.str.2025.03.010

Kazuki Kawahara, Hiroya Oki, Minato Iimori, Ryuki Muramoto, Tomoya Imai, Christoph Gerle, Hideki Shigematsu, Shigeaki Matsuda, Tetsuya Iida, Shota Nakamura

{"title":"High-resolution cryo-EM analysis visualizes hydrated type I and IV pilus structures from enterotoxigenic Escherichia coli","authors":"Kazuki Kawahara, Hiroya Oki, Minato Iimori, Ryuki Muramoto, Tomoya Imai, Christoph Gerle, Hideki Shigematsu, Shigeaki Matsuda, Tetsuya Iida, Shota Nakamura","doi":"10.1016/j.str.2025.03.010","DOIUrl":"https://doi.org/10.1016/j.str.2025.03.010","url":null,"abstract":"Pathogenic bacteria utilize a variety of pilus filaments to colonize intestinal epithelia, including those synthesized by the chaperone-usher or type IV pilus assembly pathway. Despite the importance of these filaments as potential drug and vaccine targets, their large size and dynamic nature make high-resolution structure determination challenging. Here, we used cryo-electron microscopy (cryo-EM) and whole-genome sequencing to determine the structures of type I and IV pili expressed in enterotoxigenic Escherichia coli. Well-defined cryo-EM maps at resolutions of 2.2 and 1.8 Å for type I and IV pilus, respectively, facilitated the de novo structural modeling for these filaments, revealing side-chain structures in detail. We resolved thousands of hydrated water molecules around and within the inner core of the filaments, which stabilize the otherwise metastable quaternary subunit assembly. The high-resolution structures offer novel insights into subunit-subunit interactions, and provide important clues to understand pilus assembly, stability, and flexibility.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"165 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143820089","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 the assembly and regulation of 2′-O RNA methylation by SARS-CoV-2 nsp16/nsp10 SARS-CoV-2 nsp16/nsp10组装和调控2 ' -O RNA甲基化的结构见解

IF 5.7 2区生物学

Structure Pub Date : 2025-04-11 DOI: 10.1016/j.str.2025.03.009

Anurag Misra, R. Rahisuddin, Manish Parihar, Shailee Arya, Thiruselvam Viswanathan, Nathaniel Jackson, Shan Qi, Siu-Hong Chan, Reuben S. Harris, Luis Martinez-Sobrido, Yogesh K. Gupta

{"title":"Structural insights into the assembly and regulation of 2′-O RNA methylation by SARS-CoV-2 nsp16/nsp10","authors":"Anurag Misra, R. Rahisuddin, Manish Parihar, Shailee Arya, Thiruselvam Viswanathan, Nathaniel Jackson, Shan Qi, Siu-Hong Chan, Reuben S. Harris, Luis Martinez-Sobrido, Yogesh K. Gupta","doi":"10.1016/j.str.2025.03.009","DOIUrl":"https://doi.org/10.1016/j.str.2025.03.009","url":null,"abstract":"2′-O-ribose methylation of the first transcribed base (adenine or A1 in SARS-CoV-2) of viral RNA mimics host RNAs and subverts the innate immune response. How nsp16, with partner nsp10, assembles on the 5′-end of SARS-CoV-2 mRNA to methylate A1 is not fully understood. We present a ∼2.4 Å crystal structure of the heterotetrameric complex formed by the cooperative assembly of two nsp16/nsp10 heterodimers with one 10-mer Cap-1 RNA (product) bound to each. An aromatic zipper-like motif in nsp16 and the N-terminal regions of nsp10 and nsp16 orchestrate oligomeric assembly for efficient methylation. The front catalytic pocket of nsp16 stabilizes the upstream portion of the RNA while downstream RNA remains unresolved, likely due to flexibility. An inverted nsp16 dimer extends the positively charged surface for longer RNA to influence catalysis. Additionally, a non-specific nucleotide-binding pocket on the backside of nsp16 plays a critical role in catalysis, contributing to enzymatic activity.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"21 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143820088","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

RQC2 is a major player in peptide release from stalled ribosomes RQC2是停止核糖体释放肽的主要参与者

IF 5.7 2区生物学

Structure Pub Date : 2025-04-04 DOI: 10.1016/j.str.2025.03.008

Céline Fabret, Emmanuel Giudice, Sophie Chat, Reynald Gillet, Olivier Namy

引用次数: 0

A tale of detergent tails: GPCR activation beyond ligands 洗涤剂尾部的故事：GPCR在配体之外的激活

IF 5.7 2区生物学

Structure Pub Date : 2025-04-03 DOI: 10.1016/j.str.2025.03.005

Eugene Agyemang, Rajan Lamichhane

引用次数: 0

Spy-ing on nucleic acids: Atomic resolution of the S. pyogenes CRISPR-Cas9 surveillance state 核酸间谍：化脓性链球菌CRISPR-Cas9监测状态的原子分辨率