Structure最新文献_第6页

PROTAC-mediated activation, rather than degradation, of a nuclear receptor reveals complex ligand-receptor interaction network PROTAC 介导的核受体激活而非降解揭示了复杂的配体-受体相互作用网络

IF 5.7 2区生物学

Structure Pub Date : 2024-10-09 DOI: 10.1016/j.str.2024.09.016

Andrew D. Huber, Wenwei Lin, Shyaron Poudel, Darcie J. Miller, Taosheng Chen

{"title":"PROTAC-mediated activation, rather than degradation, of a nuclear receptor reveals complex ligand-receptor interaction network","authors":"Andrew D. Huber, Wenwei Lin, Shyaron Poudel, Darcie J. Miller, Taosheng Chen","doi":"10.1016/j.str.2024.09.016","DOIUrl":"https://doi.org/10.1016/j.str.2024.09.016","url":null,"abstract":"Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules containing a ligand for a protein of interest linked to an E3 ubiquitin ligase ligand that induce protein degradation through E3 recruitment to the target protein. Small changes in PROTAC linkers can have drastic consequences, including loss of degradation activity, but the structural mechanisms governing such changes are unclear. To study this phenomenon, we screened PROTACs of diverse targeting modalities and identified dTAG-13 as an activator of the xenobiotic-sensing pregnane X receptor (PXR), which promiscuously binds various ligands. Characterization of dTAG-13 analogs and precursors revealed interplay between the PXR-binding moiety, linker, and E3 ligand that altered PXR activity without inducing degradation. A crystal structure of PXR ligand binding domain bound to a precursor ligand showed ligand-induced binding pocket distortions and a linker-punctured tunnel to the protein exterior at a region incompatible with E3 complex formation, highlighting the effects of linker environment on PROTAC activity.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"8 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385777","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 Clostridium perfringens enterotoxin bound to its human receptor, claudin-4 产气荚膜梭菌肠毒素与其人类受体 Claudin-4 结合的冷冻电子显微镜结构

IF 5.7 2区生物学

Structure Pub Date : 2024-10-08 DOI: 10.1016/j.str.2024.09.015

Sewwandi S. Rathnayake, Satchal K. Erramilli, Anthony A. Kossiakoff, Alex J. Vecchio

引用次数: 0

Structural mechanism of HP1⍺-dependent transcriptional repression and chromatin compaction HP1⍺ 依赖性转录抑制和染色质压实的结构机制

IF 5.7 2区生物学

Structure Pub Date : 2024-10-08 DOI: 10.1016/j.str.2024.09.013

Vladyslava Sokolova, Jacob Miratsky, Vladimir Svetlov, Michael Brenowitz, John Vant, Tyler S. Lewis, Kelly Dryden, Gahyun Lee, Shayan Sarkar, Evgeny Nudler, Abhishek Singharoy, Dongyan Tan

{"title":"Structural mechanism of HP1⍺-dependent transcriptional repression and chromatin compaction","authors":"Vladyslava Sokolova, Jacob Miratsky, Vladimir Svetlov, Michael Brenowitz, John Vant, Tyler S. Lewis, Kelly Dryden, Gahyun Lee, Shayan Sarkar, Evgeny Nudler, Abhishek Singharoy, Dongyan Tan","doi":"10.1016/j.str.2024.09.013","DOIUrl":"https://doi.org/10.1016/j.str.2024.09.013","url":null,"abstract":"Heterochromatin protein 1 (HP1) plays a central role in establishing and maintaining constitutive heterochromatin. However, the mechanisms underlying HP1-nucleosome interactions and their contributions to heterochromatin functions remain elusive. Here, we present the cryoelectron microscopy (cryo-EM) structure of an HP1α dimer bound to an H2A.Z-nucleosome, revealing two distinct HP1α-nucleosome interfaces. The primary HP1α binding site is located at the N terminus of histone H3, specifically at the trimethylated lysine 9 (K9me3) region, while a secondary binding site is situated near histone H2B, close to nucleosome superhelical location 4 (SHL4). Our biochemical data further demonstrates that HP1α binding influences the dynamics of DNA on the nucleosome. It promotes DNA unwrapping near the nucleosome entry and exit sites while concurrently restricting DNA accessibility in the vicinity of SHL4. Our study offers a model for HP1α-mediated heterochromatin maintenance and gene silencing. It also sheds light on the H3K9me-independent role of HP1 in responding to DNA damage.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"225 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384295","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 of selective beta-carotene binding by a soluble protein 可溶性蛋白质选择性结合β-胡萝卜素的结构基础

IF 5.7 2区生物学

Structure Pub Date : 2024-10-08 DOI: 10.1016/j.str.2024.09.014

Nikita A. Egorkin, Eva E. Dominnik, Roman I. Raevskii, Daria D. Kuklina, Larisa A. Varfolomeeva, Vladimir O. Popov, Konstantin M. Boyko, Nikolai N. Sluchanko

引用次数: 0

Structural biology of the human papillomavirus 人类乳头瘤病毒的结构生物学

IF 5.7 2区生物学

Structure Pub Date : 2024-10-04 DOI: 10.1016/j.str.2024.09.011

Feng Han, Xin-ying Guo, Ming-xia Jiang, Ning-shao Xia, Ying Gu, Shao-wei Li

引用次数: 0

Predicting protein interactions of the kinase Lck critical to T cell modulation 预测对 T 细胞调控至关重要的激酶 Lck 蛋白相互作用

IF 5.7 2区生物学

Structure Pub Date : 2024-10-04 DOI: 10.1016/j.str.2024.09.010

Mu Gao, Jeffrey Skolnick

引用次数: 0

Mechanism of phospho-Ubls’ specificity and conformational changes that regulate Parkin activity 磷酸化-Ubls 的特异性和构象变化调节 Parkin 活性的机制

IF 5.7 2区生物学

Structure Pub Date : 2024-10-04 DOI: 10.1016/j.str.2024.09.012

Dipti Ranjan Lenka, Shradha Chaurasiya, Loknath Ratnakar, Atul Kumar

引用次数: 0

Conformational dynamics of SARS-CoV-2 Omicron spike trimers during fusion activation at single molecule resolution 以单分子分辨率观察 SARS-CoV-2 Omicron 穗状三聚体在融合激活过程中的构象动态

IF 5.7 2区生物学

Structure Pub Date : 2024-10-03 DOI: 10.1016/j.str.2024.09.008

Shuvankar Dey, Purba Pahari, Srija Mukherjee, James B. Munro, Dibyendu Kumar Das

{"title":"Conformational dynamics of SARS-CoV-2 Omicron spike trimers during fusion activation at single molecule resolution","authors":"Shuvankar Dey, Purba Pahari, Srija Mukherjee, James B. Munro, Dibyendu Kumar Das","doi":"10.1016/j.str.2024.09.008","DOIUrl":"https://doi.org/10.1016/j.str.2024.09.008","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron entry involves spike (S) glycoprotein-mediated fusion of viral and late endosomal membranes. Here, using single-molecule Förster resonance energy transfer (sm-FRET) imaging and biochemical measurements, we directly visualized conformational changes of individual spike trimers on the surface of SARS-CoV-2 Omicron pseudovirions during fusion activation. We observed that the S2 domain of the Omicron spike is a dynamic fusion machine. S2 reversibly interchanges between the pre-fusion conformation and two previously undescribed intermediate conformations. Acidic pH shifts the conformational equilibrium of S2 toward an intermediate conformation and promotes the membrane hemi-fusion reaction. Moreover, we captured conformational reversibility in the S2 domain, which suggests that spike can protect itself from pre-triggering. Furthermore, we determined that Ca<sup>2+</sup> directly promotes the S2 conformational change from an intermediate conformation to post-fusion conformation. In the presence of a target membrane, low pH and Ca<sup>2+</sup> stimulate the irreversible transition to S2 post-fusion state and promote membrane fusion.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"222 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142369154","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

Crystal structure of blue laccase BP76, a unique termite suicidal defense weapon. 一种独特的白蚁自杀式防御武器--蓝色漆酶 BP76 的晶体结构。

IF 4.4 2区生物学

Structure Pub Date : 2024-10-03 Epub Date: 2024-08-15 DOI: 10.1016/j.str.2024.07.015

Jana Škerlová, Jiří Brynda, Jan Šobotník, Marek Zákopčaník, Petr Novák, Thomas Bourguignon, David Sillam-Dussès, Pavlína Řezáčová

引用次数: 0

A BTB extension and ion-binding domain contribute to the pentameric structure and TFAP2A binding of KCTD1. BTB 扩展域和离子结合域有助于 KCTD1 的五聚体结构和 TFAP2A 结合。

IF 4.4 2区生物学

Structure Pub Date : 2024-10-03 Epub Date: 2024-08-26 DOI: 10.1016/j.str.2024.07.023

Daniel M Pinkas, Joshua C Bufton, Alice E Hunt, Charlotte E Manning, William Richardson, Alex N Bullock

引用次数: 0