IF 5.7 2区生物学

Structure Pub Date : 2025-07-11 DOI: 10.1016/j.str.2025.06.006

Kirill Kovalev, Artem Stetsenko, Florian Trunk, Egor Marin, Jose M. Haro-Moreno, Gerrit H.U. Lamm, Alexey Alekseev, Francisco Rodriguez-Valera, Thomas R. Schneider, Josef Wachtveitl, Albert Guskov

{"title":"Structural basis for no retinal binding in flotillin-associated rhodopsins","authors":"Kirill Kovalev, Artem Stetsenko, Florian Trunk, Egor Marin, Jose M. Haro-Moreno, Gerrit H.U. Lamm, Alexey Alekseev, Francisco Rodriguez-Valera, Thomas R. Schneider, Josef Wachtveitl, Albert Guskov","doi":"10.1016/j.str.2025.06.006","DOIUrl":"https://doi.org/10.1016/j.str.2025.06.006","url":null,"abstract":"Rhodopsins are light-sensitive membrane proteins capturing solar energy via a retinal cofactor covalently attached to a lysine residue. Several groups of rhodopsins lack the conserved lysine and showed no retinal binding. Recently, flotillin-associated rhodopsins (FArhodopsins or FARs) were identified and suggested to lack the retinal-binding pocket despite preserving the lysine residue in many members of the group. Here, we present cryoelectron microscopic (cryo-EM) structures of paralog FArhodopsin and proteorhodopsin from marine bacterium <em>Pseudothioglobus</em>, both forming pentamers similar to those of other microbial rhodopsins. We demonstrate no binding of retinal to the FArhodopsin despite preservation of the lysine residue and overall similarity of the protein fold and internal organization to those of the retinal-binding paralog. Mutational analysis confirmed that two amino acids, H84 and E120, prevent retinal binding within the FArhodopsin. Our work provides insights into the natural retinal loss in microbial rhodopsins and might contribute to the further understanding of FArhodopsins.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"35 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602982","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

Structures of USP7 in active and inactive states bound to DNMT1 revealed by cryo-EM 低温电镜显示USP7与DNMT1结合的活性和非活性结构

IF 5.7 2区生物学

Structure Pub Date : 2025-07-10 DOI: 10.1016/j.str.2025.06.005

Nao Nakamura, Sae Yoshimi, Amika Kikuchi, Hiroki Onoda, Satomi Kori, Makoto Nakanishi, Atsuya Nishiyama, Kyohei Arita

{"title":"Structures of USP7 in active and inactive states bound to DNMT1 revealed by cryo-EM","authors":"Nao Nakamura, Sae Yoshimi, Amika Kikuchi, Hiroki Onoda, Satomi Kori, Makoto Nakanishi, Atsuya Nishiyama, Kyohei Arita","doi":"10.1016/j.str.2025.06.005","DOIUrl":"https://doi.org/10.1016/j.str.2025.06.005","url":null,"abstract":"The ubiquitin signal generated by UHRF1 is essential for DNA methylation maintenance by recruiting DNA methyltransferase 1 (DNMT1) to hemimethylated DNA through strong binding of its replication foci targeting sequence (RFTS) domain to ubiquitinated histone H3. The ubiquitin-specific protease 7 (USP7) forms a complex with DNMT1 and removes ubiquitin from H3. However, it remains unknown how USP7 deubiquitinates ubiquitinated H3 upon strong binding of the DNMT1 RFTS domain. Here, we show the activation mechanism of USP7 by combining biochemical and structural studies. USP7 is inactive toward ubiquitinated H3 in complex with the RFTS domain. However, when complexed with DNMT1, USP7 efficiently deubiquitinates ubiquitinated H3. Cryogenic electron microscopy (cryo-EM) single particle analysis revealed that USP7 bound to DNMT1 undergoes an open (inactive) and closed (active) conformational transition. Our findings provide mechanistic insights into the activation of USP7 upon binding to DNMT1 and contribute to a better understanding of the deubiquitination process in DNA methylation maintenance.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"11 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594756","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

Structure of a type II SMC Wadjet complex from Neobacillus vireti 病毒新杆菌II型SMC Wadjet复合物的结构

IF 5.7 2区生物学

Structure Pub Date : 2025-07-07 DOI: 10.1016/j.str.2025.06.004

Florian Roisné-Hamelin, Hon Wing Liu, Stephan Gruber

引用次数: 0

Elucidating PTEN conformational dynamics and phosphatase regulation via integrative modeling and mutation prediction 通过综合建模和突变预测阐明PTEN构象动力学和磷酸酶调控

IF 5.7 2区生物学

Structure Pub Date : 2025-07-03 DOI: 10.1016/j.str.2025.06.002

Jennifer Erin Dawson, Iris Nira Smith, Ann Marie Tushar, Charis Eng

引用次数: 0

AI-guided cryo-EM analysis untangles uromodulin lattices that safeguard kidneys 人工智能引导的低温电镜分析解开了保护肾脏的尿调蛋白晶格

IF 5.7 2区生物学

Structure Pub Date : 2025-07-03 DOI: 10.1016/j.str.2025.06.003

Kelvin Han Chung Chong, Bin Wu

引用次数: 0

Decoding the molecular choreography of colibactin: Structural insights into a genotoxic assembly line 解码大肠杆菌蛋白的分子编排：基因毒性装配线的结构洞察

IF 5.7 2区生物学

Structure Pub Date : 2025-07-03 DOI: 10.1016/j.str.2025.06.001

Dandan Li, Zhijun Wang

引用次数: 0

Modeling phase separation of biomolecular condensates with data-driven mass-conserving reaction-diffusion systems 用数据驱动的质量守恒反应-扩散系统模拟生物分子凝聚物的相分离

IF 5.7 2区生物学

Structure Pub Date : 2025-06-25 DOI: 10.1016/j.str.2025.05.018

Cheng Li, Man-Ting Guo, Xiaoqing He, Quan-Xing Liu, Zhi Qi

引用次数: 0

Structural insights into the biotechnologically relevant reversible NADPH-oxidizing NiFe-hydrogenase from P. furiosus 从P. furiosus生物技术相关可逆nadph氧化nife -氢化酶的结构见解

IF 5.7 2区生物学

Structure Pub Date : 2025-06-25 DOI: 10.1016/j.str.2025.05.017

Xiansha Xiao, Gerrit J. Schut, Xiang Feng, Patrick M. McTernan, Dominik K. Haja, William N. Lanzilotta, Michael W.W. Adams, Huilin Li

引用次数: 0

Targeting ceramide synthases for the development of new antifungals 以神经酰胺合酶为靶点开发新型抗真菌药物

IF 5.7 2区生物学

Structure Pub Date : 2025-06-23 DOI: 10.1016/j.str.2025.05.016

Deveney Dasilva, Nivea Pereira de Sa, Kathryn Takemura, Kalani Jayanetti, Jeehyun Karen You, Nathalia Vieira de Sa, Gabriel Soares Matos, Andy Zhong, Can E. Senkal, Yusuf Hannun, Iwao Ojima, John Mallamo, John B. McCarthy, Maurizio Del Poeta

{"title":"Targeting ceramide synthases for the development of new antifungals","authors":"Deveney Dasilva, Nivea Pereira de Sa, Kathryn Takemura, Kalani Jayanetti, Jeehyun Karen You, Nathalia Vieira de Sa, Gabriel Soares Matos, Andy Zhong, Can E. Senkal, Yusuf Hannun, Iwao Ojima, John Mallamo, John B. McCarthy, Maurizio Del Poeta","doi":"10.1016/j.str.2025.05.016","DOIUrl":"https://doi.org/10.1016/j.str.2025.05.016","url":null,"abstract":"Invasive fungal infections (IFIs) caused by pathogenic fungi are a major public health concern, particularly across various immunocompromised populations. Effective clinical management is currently hindered by limited treatment options. Fungal sphingolipids have emerged as potential antifungal targets based on cumulative evidence demonstrating that fungal sphingolipid metabolism is key to the virulence of pathogenic fungi. This study focuses on the sphingolipid metabolizing enzyme ceramide synthase. We developed an enzymatic assay to examine ceramide synthase activity and devised a high-throughput screening platform. Two synthetic compounds were identified that preferentially inhibit the fungal vs. the mammalian ceramide synthase activity. Further studies indicate that these compounds block fungal growth, with <em>in silico</em> and mutagenesis investigations revealing insights into the interactions between the inhibitors and the ceramide synthase active site. Together, our study establishes fungal ceramide synthase as a promising antifungal target and paves the way for new structure-activity relationship studies leveraging fungal sphingolipid metabolism.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"15 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341288","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

Rapid hepatitis C virus replication machinery removal after antiviral treatment with DAA monitored by multimodal imaging 多模态成像监测的DAA抗病毒治疗后丙型肝炎病毒复制机制的快速清除

IF 5.7 2区生物学

Structure Pub Date : 2025-06-18 DOI: 10.1016/j.str.2025.05.015

Victoria Castro, Gema Calvo, Ana J. Pérez-Berná, Kevin Mamprin, Sergey Kapishnikov, David Rogers, Stephen O'Connor, Paul Sheridan, Kenneth Fahy, Eva Pereiro, Pablo Gastaminza

{"title":"Rapid hepatitis C virus replication machinery removal after antiviral treatment with DAA monitored by multimodal imaging","authors":"Victoria Castro, Gema Calvo, Ana J. Pérez-Berná, Kevin Mamprin, Sergey Kapishnikov, David Rogers, Stephen O'Connor, Paul Sheridan, Kenneth Fahy, Eva Pereiro, Pablo Gastaminza","doi":"10.1016/j.str.2025.05.015","DOIUrl":"https://doi.org/10.1016/j.str.2025.05.015","url":null,"abstract":"Hepatitis C virus (HCV) replication causes a profound remodeling of the host endomembrane system. The availability of direct-acting antiviral (DAA) drugs provides an opportunity to define the ultrastructural events that follow viral replication blockade using confocal immunofluorescence, transmission electron microscopy (TEM) as well as correlative cryogenic light-soft X-ray tomography (CLSXT). Study of DAA-treated HCV replicons using CLSXT indicates that HCV-induced membranous alterations are no longer visible after 24 h of treatment and that a component of the replicase is located in pleomorphic, high-absorption contrast acidic organelles. TEM studies confirmed the rapid elimination of the viral machinery, and the concurrent appearance of large endo-lysosomes in DAA-treated cells. These and results by others suggest that HCV replication compartment may constantly be recycled by the endo-lysosomal system and that this equilibrium is unbalanced by DAA treatment, resulting in a transient activation of the endo-lysosomal system to achieve rapid viral machinery removal.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"12 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311687","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

Structure最新文献