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PARG inhibition induces nuclear aggregation of PARylated PARP1 PARG 抑制可诱导 PARylated PARP1 的核聚集

IF 5.7 2区生物学

Structure Pub Date : 2024-10-14 DOI: 10.1016/j.str.2024.09.006

Sateja Paradkar, Julia Purcell, Annie Cui, Sam Friedman, Katelyn J. Noronha, Matthew A. Murray, Ranjini K. Sundaram, Ranjit S. Bindra, Ryan B. Jensen

引用次数: 0

Structural basis for the ligand promiscuity of the hydroxamate siderophore binding protein FtsB from Streptococcus pyogenes 化脓性链球菌中的羟基氨基甲酸酯苷元结合蛋白 FtsB 的配体杂合性的结构基础

IF 5.7 2区生物学

Structure Pub Date : 2024-10-11 DOI: 10.1016/j.str.2024.09.018

Jorge Fernandez-Perez, Akinobu Senoo, Jose M.M. Caaveiro, Makoto Nakakido, Susana de Vega, Ichiro Nakagawa, Kouhei Tsumoto

{"title":"Structural basis for the ligand promiscuity of the hydroxamate siderophore binding protein FtsB from Streptococcus pyogenes","authors":"Jorge Fernandez-Perez, Akinobu Senoo, Jose M.M. Caaveiro, Makoto Nakakido, Susana de Vega, Ichiro Nakagawa, Kouhei Tsumoto","doi":"10.1016/j.str.2024.09.018","DOIUrl":"https://doi.org/10.1016/j.str.2024.09.018","url":null,"abstract":"Pathogenic bacteria must secure the uptake of nutritional metals such as iron for their growth, making their import systems attractive targets for the development of new antimicrobial modalities. In the pathogenic bacterium Streptococcus pyogenes, the iron uptake system FtsABCD transports iron encapsulated by siderophores of the hydroxamate class. However, the inability of S. pyogenes to produce these metabolites makes the biological and clinical relevance of this route unresolved. Herein, we demonstrated that the periplasmic binding protein FtsB recognizes not only the hydroxamate siderophore ferrichrome, as previously documented, but also ferrioxamine E (FOE), ferrioxamine B (FOB), and bisucaberin (BIS), each of them with high affinity (nM level). Up to seven aromatic residues in the binding pocket accommodate the variable backbones of the different siderophores through CH-π interactions, explaining ligand promiscuity. Collectively, our observations revealed how S. pyogenes exploits the diverse xenosiderophores produced by other microorganisms as iron sources to secure this precious nutrient.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"13 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405131","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 dissection of the CMP-pseudaminic acid synthetase, PseF CMP 伪氨基酸合成酶 PseF 的结构剖析

IF 5.7 2区生物学

Structure Pub Date : 2024-10-10 DOI: 10.1016/j.str.2024.09.017

Tessa Keenan, Andrew R. Cowan, Emily K.P. Flack, Natasha E. Hatton, Abigail J. Walklett, Gavin H. Thomas, Glyn R. Hemsworth, Martin A. Fascione

引用次数: 0

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