发布求助
文献互助 智能选刊 最新文献

Current opinion in structural biology最新文献

筛选
英文 中文
Structures and compositional dynamics of Mediator in transcription regulation 转录调控中 Mediator 的结构和组成动态。
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-07-26 DOI: 10.1016/j.sbi.2024.102892
Tao Li, Ti-Chun Chao, Kuang-Lei Tsai
{"title":"Structures and compositional dynamics of Mediator in transcription regulation","authors":"Tao Li,&nbsp;Ti-Chun Chao,&nbsp;Kuang-Lei Tsai","doi":"10.1016/j.sbi.2024.102892","DOIUrl":"10.1016/j.sbi.2024.102892","url":null,"abstract":"<div><p>The eukaryotic Mediator, comprising a large Core (cMED) and a dissociable CDK8 kinase module (CKM), functions as a critical coregulator during RNA polymerase II (RNAPII) transcription. cMED recruits RNAPII and facilitates the assembly of the pre-initiation complex (PIC) at promoters. In contrast, CKM prevents RNAPII binding to cMED while simultaneously exerting positive or negative influence on gene transcription through its kinase function. Recent structural studies on cMED and CKM have revealed their intricate architectures and subunit interactions. Here, we explore these structures, providing a comprehensive insight into Mediator (cMED-CKM) architecture and its potential mechanism in regulating RNAPII transcription. Additionally, we discuss the remaining puzzles that require further investigation to fully understand how cMED coordinates with CKM to regulate transcription in various events.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"88 ","pages":"Article 102892"},"PeriodicalIF":6.1,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959440X24001192/pdfft?md5=10fec5f8a1c983ec13ee4b17d387ccba&pid=1-s2.0-S0959440X24001192-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Beyond ligand binding: Single molecule observation reveals how riboswitches integrate multiple signals to balance bacterial gene regulation 超越配体结合：单分子观察揭示了核糖开关如何整合多种信号以平衡细菌基因调控。
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-07-26 DOI: 10.1016/j.sbi.2024.102893
Adrien Chauvier, Nils G. Walter
{"title":"Beyond ligand binding: Single molecule observation reveals how riboswitches integrate multiple signals to balance bacterial gene regulation","authors":"Adrien Chauvier,&nbsp;Nils G. Walter","doi":"10.1016/j.sbi.2024.102893","DOIUrl":"10.1016/j.sbi.2024.102893","url":null,"abstract":"<div><p>Riboswitches are specialized RNA structures that orchestrate gene expression in response to sensing specific metabolite or ion ligands, mostly in bacteria. Upon ligand binding, these conformationally dynamic RNA motifs undergo structural changes that control critical gene expression processes such as transcription termination and translation initiation, thereby enabling cellular homeostasis and adaptation. Because RNA folds rapidly and co-transcriptionally, riboswitches make use of the low complexity of RNA sequences to adopt alternative, transient conformations on the heels of the transcribing RNA polymerase (RNAP), resulting in kinetic partitioning that defines the regulatory outcome. This review summarizes single molecule microscopy evidence that has begun to unveil a sophisticated network of dynamic, kinetically balanced interactions between riboswitch architecture and the gene expression machinery that, together, integrate diverse cellular signals.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"88 ","pages":"Article 102893"},"PeriodicalIF":6.1,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787470","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
Death at a funeral: Activation of the dead enzyme, MLKL, to kill cells by necroptosis 葬礼上的死亡激活死亡酶 MLKL，通过坏死作用杀死细胞。
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-07-25 DOI: 10.1016/j.sbi.2024.102891
Katherine A. Davies , Peter E. Czabotar , James M. Murphy
{"title":"Death at a funeral: Activation of the dead enzyme, MLKL, to kill cells by necroptosis","authors":"Katherine A. Davies ,&nbsp;Peter E. Czabotar ,&nbsp;James M. Murphy","doi":"10.1016/j.sbi.2024.102891","DOIUrl":"10.1016/j.sbi.2024.102891","url":null,"abstract":"<div><p>Necroptosis is a lytic form of programmed cell death implicated in inflammatory pathologies, leading to intense interest in the underlying mechanisms and therapeutic prospects. Here, we review our current structural understanding of how the terminal executioner of the pathway, the dead kinase, mixed lineage kinase domain-like (MLKL), is converted from a dormant to killer form by the upstream regulatory kinase, RIPK3. RIPK3-mediated phosphorylation of MLKL's pseudokinase domain toggles a molecular switch that induces dissociation from a cytoplasmic platform, assembly of MLKL oligomers, and trafficking to the plasma membrane, where activated MLKL accumulates and permeabilises the lipid bilayer to induce cell death. We highlight gaps in mechanistic knowledge of MLKL's activation, how mechanisms diverge between species, and the power of modelling in advancing structural insights.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"88 ","pages":"Article 102891"},"PeriodicalIF":6.1,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959440X24001180/pdfft?md5=6d931814dc4980e4f60216073440c7c3&pid=1-s2.0-S0959440X24001180-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ion-driven rotary membrane motors: From structure to function 离子驱动旋转膜马达：从结构到功能
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-07-24 DOI: 10.1016/j.sbi.2024.102884
Freddie J.O. Martin, Mònica Santiveri , Haidai Hu , Nicholas M.I. Taylor
{"title":"Ion-driven rotary membrane motors: From structure to function","authors":"Freddie J.O. Martin,&nbsp;Mònica Santiveri ,&nbsp;Haidai Hu ,&nbsp;Nicholas M.I. Taylor","doi":"10.1016/j.sbi.2024.102884","DOIUrl":"10.1016/j.sbi.2024.102884","url":null,"abstract":"<div><p>Ion-driven membrane motors, essential across all domains of life, convert a gradient of ions across a membrane into rotational energy, facilitating diverse biological processes including ATP synthesis, substrate transport, and bacterial locomotion. Herein, we highlight recent structural advances in the understanding of two classes of ion-driven membrane motors: rotary ATPases and 5:2 motors. The recent structure of the human F-type ATP synthase is emphasised along with the gained structural insight into clinically relevant mutations. Furthermore, we highlight the diverse roles of 5:2 motors and recent mechanistic understanding gained through the resolution of ions in the structure of a sodium-driven motor, combining insights into potential unifying mechanisms of ion selectivity and rotational torque generation in the context of their function as part of complex biological systems.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"88 ","pages":"Article 102884"},"PeriodicalIF":6.1,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959440X24001118/pdfft?md5=3d420fd977d0790fe93a91624256205e&pid=1-s2.0-S0959440X24001118-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the conformational landscape of protein kinases 探索蛋白激酶的构象图谱
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-07-22 DOI: 10.1016/j.sbi.2024.102890
Nancy R. Gough, Charalampos G. Kalodimos
{"title":"Exploring the conformational landscape of protein kinases","authors":"Nancy R. Gough,&nbsp;Charalampos G. Kalodimos","doi":"10.1016/j.sbi.2024.102890","DOIUrl":"10.1016/j.sbi.2024.102890","url":null,"abstract":"<div><p>Protein kinases are dynamic enzymes that display complex regulatory mechanisms. Although they possess a structurally conserved catalytic domain, significant conformational dynamics are evident both within a single kinase and across different kinases in the kinome. Here, we highlight methods for exploring this conformational space and its dynamics using kinase domains from ABL1 (Abelson kinase), PKA (protein kinase A), AurA (Aurora A), and PYK2 (proline-rich tyrosine kinase 2) as examples. Such experimental approaches combined with AI-driven methods, such as AlphaFold, will yield discoveries about kinase regulation, the catalytic process, substrate specificity, the effect of disease-associated mutations, as well as new opportunities for structure-based drug design.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"88 ","pages":"Article 102890"},"PeriodicalIF":6.1,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736724","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
Dynamics in Cre-loxP site-specific recombination Cre-loxP 位点特异性重组的动态变化
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-07-18 DOI: 10.1016/j.sbi.2024.102878
Mark P. Foster, Matthew J. Benedek, Tyler D. Billings, Jonathan S. Montgomery
{"title":"Dynamics in Cre-loxP site-specific recombination","authors":"Mark P. Foster,&nbsp;Matthew J. Benedek,&nbsp;Tyler D. Billings,&nbsp;Jonathan S. Montgomery","doi":"10.1016/j.sbi.2024.102878","DOIUrl":"10.1016/j.sbi.2024.102878","url":null,"abstract":"<div><p>Cre recombinase is a phage-derived enzyme that has found utility for precise manipulation of DNA sequences. Cre recognizes and recombines pairs of <em>loxP</em> sequences characterized by an inverted repeat and asymmetric spacer. Cre cleaves and religates its DNA targets such that error-prone repair pathways are not required to generate intact DNA products. Major obstacles to broader applications are lack of knowledge of how Cre recognizes its targets, and how its activity is controlled. The picture emerging from high resolution methods is that the dynamic properties of both the enzyme and its DNA target are important determinants of its activity in both sequence recognition and DNA cleavage. Improved understanding of the role of dynamics in the key steps along the pathway of Cre-<em>loxP</em> recombination should significantly advance our ability to both redirect Cre to new sequences and to control its DNA cleavage activity in the test tube and in cells.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"88 ","pages":"Article 102878"},"PeriodicalIF":6.1,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959440X24001052/pdfft?md5=9e745023813d113b6de70407b1fbd474&pid=1-s2.0-S0959440X24001052-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biomolecular simulations at the exascale: From drug design to organelles and beyond 超大规模生物分子模拟：从药物设计到细胞器及其他
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-07-18 DOI: 10.1016/j.sbi.2024.102887
Vytautas Gapsys , Wojciech Kopec , Dirk Matthes , Bert L. de Groot
{"title":"Biomolecular simulations at the exascale: From drug design to organelles and beyond","authors":"Vytautas Gapsys ,&nbsp;Wojciech Kopec ,&nbsp;Dirk Matthes ,&nbsp;Bert L. de Groot","doi":"10.1016/j.sbi.2024.102887","DOIUrl":"10.1016/j.sbi.2024.102887","url":null,"abstract":"<div><p>The rapid advancement in computational power available for research offers to bring not only quantitative improvements, but also qualitative changes in the field of biomolecular simulation. Here, we review the state of biomolecular dynamics simulations at the threshold to exascale resources becoming available. Both developments in parallel and distributed computing will be discussed, providing a perspective on the state of the art of both. A main focus will be on obtaining binding and conformational free energies, with an outlook to macromolecular complexes and (sub)cellular assemblies.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"88 ","pages":"Article 102887"},"PeriodicalIF":6.1,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959440X24001143/pdfft?md5=2b578ad583b2ee9d85875c616c70f9c2&pid=1-s2.0-S0959440X24001143-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Visualizing RNA structure ensembles by single-molecule correlated chemical probing 通过单分子相关化学探针观察 RNA 结构组合
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-07-17 DOI: 10.1016/j.sbi.2024.102877
J. Winston Arney , Alain Laederach , Kevin M. Weeks
{"title":"Visualizing RNA structure ensembles by single-molecule correlated chemical probing","authors":"J. Winston Arney ,&nbsp;Alain Laederach ,&nbsp;Kevin M. Weeks","doi":"10.1016/j.sbi.2024.102877","DOIUrl":"10.1016/j.sbi.2024.102877","url":null,"abstract":"<div><p>RNA molecules fold to form complex internal structures. Many of these RNA structures populate ensembles with rheostat-like properties, with each state having a distinct function. Until recently, analysis of RNA structures, especially within cells, was limited to modeling either a single averaged structure or computationally-modeled ensembles. These approaches obscure the intrinsic heterogeneity of many structured RNAs. Single-molecule correlated chemical probing (smCCP) strategies are now making it possible to measure and deconvolute RNA structure ensembles based on efficiently executed chemical probing experiments. Here, we provide an overview of fundamental single-molecule probing principles, review current ensemble deconvolution strategies, and discuss recent applications to diverse biological systems. smCCP is enabling a revolution in understanding how the plasticity of RNA structure is exploited in biological systems to respond to stimuli and alter gene function. The energetics of RNA ensembles are often subtle and a subset can likely be targeted to modulate disease-associated biological processes.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"88 ","pages":"Article 102877"},"PeriodicalIF":6.1,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636511","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
Diversity of structure and function in Cullin E3 ligases Cullin E3 连接酶结构和功能的多样性
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-07-15 DOI: 10.1016/j.sbi.2024.102879
Calvin P. Lin, Elizabeth A. Komives
{"title":"Diversity of structure and function in Cullin E3 ligases","authors":"Calvin P. Lin,&nbsp;Elizabeth A. Komives","doi":"10.1016/j.sbi.2024.102879","DOIUrl":"10.1016/j.sbi.2024.102879","url":null,"abstract":"<div><p>The cellular process by which the protein ubiquitin (Ub) is covalently attached to a protein substrate involves Ub activating (E1s) and conjugating enzymes (E2s) that work together with a large variety of E3 ligases that impart substrate specificity. The largest family of E3s is the Cullin-RING ligase (CRL) family which utilizes a wide variety of substrate receptors, adapter proteins, and cooperating ligases. Cryo-electron microscopy (cryoEM) has revealed a wide variety of structures which suggest how Ub transfer occurs. Hydrogen deuterium exchange mass spectrometry (HDXMS) has revealed the role of dynamics and expanded our knowledge of how covalent NEDD8 modification (neddylation) activates the CRLs, particularly by facilitating cooperation with additional RING-between-RING ligases to transfer Ub.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"88 ","pages":"Article 102879"},"PeriodicalIF":6.1,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959440X24001064/pdfft?md5=4d0108ead674eda244db07a4b0fdfd46&pid=1-s2.0-S0959440X24001064-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141623600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Introducing dysfunctional Protein-Protein Interactome (dfPPI) – A platform for systems-level protein-protein interaction (PPI) dysfunction investigation in disease 引入功能障碍蛋白质-蛋白质相互作用组（dfPPI）--系统级蛋白质-蛋白质相互作用（PPI）功能障碍疾病研究平台
IF 6.1 2区 生物学
Current opinion in structural biology Pub Date : 2024-07-13 DOI: 10.1016/j.sbi.2024.102886
Souparna Chakrabarty , Shujuan Wang , Tanaya Roychowdhury , Stephen D. Ginsberg , Gabriela Chiosis
{"title":"Introducing dysfunctional Protein-Protein Interactome (dfPPI) – A platform for systems-level protein-protein interaction (PPI) dysfunction investigation in disease","authors":"Souparna Chakrabarty ,&nbsp;Shujuan Wang ,&nbsp;Tanaya Roychowdhury ,&nbsp;Stephen D. Ginsberg ,&nbsp;Gabriela Chiosis","doi":"10.1016/j.sbi.2024.102886","DOIUrl":"https://doi.org/10.1016/j.sbi.2024.102886","url":null,"abstract":"<div><p>Protein-protein interactions (PPIs) play a crucial role in cellular function and disease manifestation, with dysfunctions in PPI networks providing a direct link between stressors and phenotype. The dysfunctional Protein-Protein Interactome (dfPPI) platform, formerly known as epichaperomics, is a newly developed chemoproteomic method aimed at detecting dynamic changes at the systems level in PPI networks under stressor-induced cellular perturbations within disease states. This review provides an overview of dfPPIs, emphasizing the novel methodology, data analytics, and applications in disease research. dfPPI has applications in cancer research, where it identifies dysfunctions integral to maintaining malignant phenotypes and discovers strategies to enhance the efficacy of current therapies. In neurodegenerative disorders, dfPPI uncovers critical dysfunctions in cellular processes and stressor-specific vulnerabilities. Challenges, including data complexity and the potential for integration with other omics datasets are discussed. The dfPPI platform is a potent tool for dissecting disease systems biology by directly informing on dysfunctions in PPI networks and holds promise for advancing disease identification and therapeutics.</p></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"88 ","pages":"Article 102886"},"PeriodicalIF":6.1,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959440X24001131/pdfft?md5=ce1626c6a05f554e967c55418222e73c&pid=1-s2.0-S0959440X24001131-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141606930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
首页 上一页 下一页 尾页
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整，为了账户安全，请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们：info@booksci.cn Book学术提供免费学术资源搜索服务，方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号：481959085
Book学术官方微信