Structure最新文献_第7页

Does the structure of transthyretin amyloid fibrils vary depending on the organ of accumulation? 转甲状腺素淀粉样原纤维的结构是否因器官的积累而异？

IF 5.7 2区生物学

Structure Pub Date : 2024-12-05 DOI: 10.1016/j.str.2024.11.002

Mineyuki Mizuguchi

引用次数: 0

A finger that gets in the way: When binding isn’t just about the bound state 一个碍手碍脚的手指：当绑定不仅仅是绑定状态时

IF 5.7 2区生物学

Structure Pub Date : 2024-12-05 DOI: 10.1016/j.str.2024.11.001

David Neuhaus, Katherine Stott

引用次数: 0

Structures of TASK-1 and TASK-3 K2P channels provide insight into their gating and dysfunction in disease 任务-1和任务-3 K2P通道的结构提供了对其门控和疾病功能障碍的深入了解

IF 5.7 2区生物学

Structure Pub Date : 2024-12-04 DOI: 10.1016/j.str.2024.11.005

Peter Rory Hall, Thibault Jouen-Tachoire, Marcus Schewe, Peter Proks, Thomas Baukrowitz, Elisabeth P. Carpenter, Simon Newstead, Karin E.J. Rödström, Stephen J. Tucker

{"title":"Structures of TASK-1 and TASK-3 K2P channels provide insight into their gating and dysfunction in disease","authors":"Peter Rory Hall, Thibault Jouen-Tachoire, Marcus Schewe, Peter Proks, Thomas Baukrowitz, Elisabeth P. Carpenter, Simon Newstead, Karin E.J. Rödström, Stephen J. Tucker","doi":"10.1016/j.str.2024.11.005","DOIUrl":"https://doi.org/10.1016/j.str.2024.11.005","url":null,"abstract":"TASK-1 and TASK-3 are pH-sensitive two-pore domain (K2P/KCNK) K+ channels. Their functional roles make them promising targets for treatment of multiple disorders including sleep apnea, pain, and atrial fibrillation. Mutations in these channels are also associated with neurodevelopmental and hypertensive disorders. A previous crystal structure of TASK-1 revealed a lower “X-gate” as a hotspot for missense gain-of-function (GoF) mutations associated with DDSA (developmental delay with sleep apnea). However, the mechanisms of gating in TASK channels are still not fully understood. Here, we resolve structures for both human TASK-1 and TASK-3 by cryoelectron microscopy (cryo-EM), as well as a recurrent TASK-3 variant (G236R) associated with KCNK9 imprinting syndrome (KIS) (formerly known as Birk-Barel syndrome). Combined with functional studies of the X-gating mechanism, we provide evidence for how a highly conserved gating mechanism becomes defective in disease, and also provide further insight into the pathway of conformational changes that underlie the pH-dependent inhibition of TASK channel activity.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"37 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142763464","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

Unveiling the structural proteome of an Alzheimer’s disease rat brain model 揭示阿尔茨海默病大鼠脑模型的结构蛋白质组

IF 5.7 2区生物学

Structure Pub Date : 2024-11-29 DOI: 10.1016/j.str.2024.11.004

Elnaz Khalili Samani, S.M. Naimul Hasan, Matthew Waas, Alexander F.A. Keszei, Xiaoxiao Xu, Mahtab Heydari, Mary Elizabeth Hill, JoAnne McLaurin, Thomas Kislinger, Mohammad T. Mazhab-Jafari

{"title":"Unveiling the structural proteome of an Alzheimer’s disease rat brain model","authors":"Elnaz Khalili Samani, S.M. Naimul Hasan, Matthew Waas, Alexander F.A. Keszei, Xiaoxiao Xu, Mahtab Heydari, Mary Elizabeth Hill, JoAnne McLaurin, Thomas Kislinger, Mohammad T. Mazhab-Jafari","doi":"10.1016/j.str.2024.11.004","DOIUrl":"https://doi.org/10.1016/j.str.2024.11.004","url":null,"abstract":"Studying native protein structures at near-atomic resolution in a crowded environment presents challenges. Consequently, understanding the structural intricacies of proteins within pathologically affected tissues often relies on mass spectrometry and proteomic analysis. Here, we utilized cryoelectron microscopy (cryo-EM) and the Build and Retrieve (BaR) method to investigate protein complexes’ structural characteristics such as post-translational modification, active site occupancy, and arrested conformational state in Alzheimer’s disease (AD) using brain lysate from a rat model (TgF344-AD). Our findings reveal novel insights into the architecture of these complexes, corroborated through mass spectrometry analysis. Interestingly, it has been shown that the dysfunction of these protein complexes extends beyond AD, implicating them in cancer, as well as other neurodegenerative disorders such as Parkinson’s disease, Huntington’s disease, and schizophrenia. By elucidating these structural details, our work not only enhances our understanding of disease pathology but also suggests new avenues for future approaches in therapeutic intervention.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"9 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142742585","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

Protein translocation through α-helical channels and insertases 蛋白质通过α螺旋通道和插入酶进行转运

IF 5.7 2区生物学

Structure Pub Date : 2024-11-25 DOI: 10.1016/j.str.2024.10.032

Jingxia Chen, Xueyin Zhou, Yuqi Yang, Long Li

引用次数: 0

The kinetoplastid kinetochore protein KKT23 acetyltransferase is a structural homolog of GCN5 that acetylates the histone H2A C-terminal tail 核原生动物动点蛋白 KKT23 乙酰基转移酶是 GCN5 的结构同源物，它能使组蛋白 H2A C 端尾乙酰化

IF 5.7 2区生物学

Structure Pub Date : 2024-11-22 DOI: 10.1016/j.str.2024.10.031

Patryk Ludzia, Midori Ishii, Gauri Deák, Christos Spanos, Marcus D. Wilson, Christina Redfield, Bungo Akiyoshi

{"title":"The kinetoplastid kinetochore protein KKT23 acetyltransferase is a structural homolog of GCN5 that acetylates the histone H2A C-terminal tail","authors":"Patryk Ludzia, Midori Ishii, Gauri Deák, Christos Spanos, Marcus D. Wilson, Christina Redfield, Bungo Akiyoshi","doi":"10.1016/j.str.2024.10.031","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.031","url":null,"abstract":"The kinetochore is the macromolecular protein machine that drives chromosome segregation in eukaryotes. In an evolutionarily divergent group of organisms called kinetoplastids, kinetochores are built using a unique set of proteins (KKT1–25 and KKIP1–12). KKT23 is a constitutively localized kinetochore protein containing a C-terminal acetyltransferase domain of unknown function. Here, using X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, we have determined the structure and dynamics of the KKT23 acetyltransferase domain from Trypanosoma brucei and found that it is structurally similar to the GCN5 histone acetyltransferase domain. We find that KKT23 can acetylate the C-terminal tail of histone H2A and that knockdown of KKT23 results in decreased H2A acetylation levels in T. brucei. Finally, we have determined the crystal structure of the N-terminal region of KKT23 and shown that it interacts with KKT22. Our study provides important insights into the structure and function of the unique kinetochore acetyltransferase in trypanosomes.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"11 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690706","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 and dynamics of the active site of hen egg-white lysozyme from atomic resolution neutron crystallography 通过原子分辨率中子晶体学研究母鸡卵白溶菌酶活性位点的结构和动力学特征

IF 5.7 2区生物学

Structure Pub Date : 2024-11-21 DOI: 10.1016/j.str.2024.10.030

Joao Ramos, Valerie Laux, Sax A. Mason, Marie-Hélène Lemée, Matthew W. Bowler, Kay Diederichs, Michael Haertlein, V. Trevor Forsyth, Estelle Mossou, Sine Larsen, Annette E. Langkilde

引用次数: 0

Structural basis of signaling complex inhibition by IL-6 domain-swapped dimers IL-6 结构域互换二聚体抑制信号复合体的结构基础

IF 5.7 2区生物学

Structure Pub Date : 2024-11-19 DOI: 10.1016/j.str.2024.10.028

Anna Yudenko, Sergey Bukhdruker, Pavel Shishkin, Sergey Rodin, Anastasia Burtseva, Aleksandr Petrov, Natalia Pigareva, Alexey Sokolov, Egor Zinovev, Igor Eliseev, Alina Remeeva, Egor Marin, Alexey Mishin, Valentin Gordeliy, Ivan Gushchin, Aleksandr Ischenko, Valentin Borshchevskiy

{"title":"Structural basis of signaling complex inhibition by IL-6 domain-swapped dimers","authors":"Anna Yudenko, Sergey Bukhdruker, Pavel Shishkin, Sergey Rodin, Anastasia Burtseva, Aleksandr Petrov, Natalia Pigareva, Alexey Sokolov, Egor Zinovev, Igor Eliseev, Alina Remeeva, Egor Marin, Alexey Mishin, Valentin Gordeliy, Ivan Gushchin, Aleksandr Ischenko, Valentin Borshchevskiy","doi":"10.1016/j.str.2024.10.028","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.028","url":null,"abstract":"Interleukin-6 (IL-6) is a multifaceted cytokine essential in many immune system processes and their regulation. It also plays a key role in hematopoiesis, and in triggering the acute phase reaction. IL-6 overproduction is critical in chronic inflammation associated with autoimmune diseases like rheumatoid arthritis and contributes to cytokine storms in COVID-19 patients. Over 20 years ago, researchers proposed that IL-6, which is typically monomeric, can also form dimers via a domain-swap mechanism, with indirect evidence supporting their existence. The physiological significance of IL-6 dimers was shown in B-cell chronic lymphocytic leukemia. However, no structures have been reported so far. Here, we present the crystal structure of an IL-6 domain-swapped dimer that computational approaches could not predict. The structure explains why the IL-6 dimer is antagonistic to the IL-6 monomer in signaling complex formation and provides insights for IL-6 targeted therapies.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"13 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670678","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 ALS drug riluzole binds to the C-terminal domain of SARS-CoV-2 nucleocapsid protein and has antiviral activity ALS 药物利鲁唑与 SARS-CoV-2 核头状蛋白的 C 端结构域结合并具有抗病毒活性

IF 5.7 2区生物学

Structure Pub Date : 2024-11-13 DOI: 10.1016/j.str.2024.10.025

María Ángeles Márquez-Moñino, Clara M. Santiveri, Patricia de León, Sergio Camero, Ramón Campos-Olivas, M. Ángeles Jiménez, Margarita Sáiz, Beatriz González, José Manuel Pérez-Cañadillas

{"title":"The ALS drug riluzole binds to the C-terminal domain of SARS-CoV-2 nucleocapsid protein and has antiviral activity","authors":"María Ángeles Márquez-Moñino, Clara M. Santiveri, Patricia de León, Sergio Camero, Ramón Campos-Olivas, M. Ángeles Jiménez, Margarita Sáiz, Beatriz González, José Manuel Pérez-Cañadillas","doi":"10.1016/j.str.2024.10.025","DOIUrl":"https://doi.org/10.1016/j.str.2024.10.025","url":null,"abstract":"Nucleoproteins (N) play an essential role in virus assembly and are less prone to mutation than other viral structural proteins, making them attractive targets for drug discovery. Using an NMR fragment-based drug discovery approach, we identified the 1,3-benzothiazol-2-amine (BZT) group as a scaffold to develop potential antivirals for SARS-CoV-2 nucleocapsid (N) protein. A thorough characterization of BZT derivatives using NMR, X-ray crystallography, antiviral activity assays, and intrinsic fluorescence measurements revealed their binding in the C-terminal domain (CTD) domain of the N protein, to residues Arg 259, Trp 330, and Lys 338, coinciding with the nucleotide binding site. Our most effective compound exhibits a slightly better affinity than GTP and the ALS drug riluzole, also identified during the screening, and displays notable viral inhibition activity. A virtual screening of 218 BZT-based compounds revealed a potential extended binding site that could be exploited for the future development of new SARS-CoV-2 antivirals.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"41 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601000","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 and biochemical insights into the mechanism of the anti-CRISPR protein AcrIE3 从结构和生化角度揭示抗 CRISPR 蛋白 AcrIE3 的作用机制

IF 5.7 2区生物学

Structure Pub Date : 2024-11-13 DOI: 10.1016/j.str.2024.10.024

Jasung Koo, Gyujin Lee, Changkon Park, Hyejin Oh, Sung-Hyun Hong, Jeong-Yong Suh, Euiyoung Bae

引用次数: 0