基于接触的局部能量挫折动力学分析确定了实现 RfaH 折叠转换的关键残基。

IF 4.5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Protein Science Pub Date : 2024-10-01 DOI:10.1002/pro.5182
Jorge González-Higueras, María Inés Freiberger, Pablo Galaz-Davison, R Gonzalo Parra, César A Ramírez-Sarmiento
{"title":"基于接触的局部能量挫折动力学分析确定了实现 RfaH 折叠转换的关键残基。","authors":"Jorge González-Higueras, María Inés Freiberger, Pablo Galaz-Davison, R Gonzalo Parra, César A Ramírez-Sarmiento","doi":"10.1002/pro.5182","DOIUrl":null,"url":null,"abstract":"<p><p>Fold-switching enables metamorphic proteins to reversibly interconvert between two highly dissimilar native states to regulate their protein functions. While about 100 proteins have been identified to undergo fold-switching, unveiling the key residues behind this mechanism for each protein remains challenging. Reasoning that fold-switching in proteins is driven by dynamic changes in local energetic frustration, we combined fold-switching simulations generated using simplified structure-based models with frustration analysis to identify key residues involved in this process based on the change in the density of minimally frustrated contacts during refolding. Using this approach to analyze the fold-switch of the bacterial transcription factor RfaH, we identified 20 residues that significantly change their frustration during its fold-switch, some of which have been experimentally and computationally reported in previous works. Our approach, which we developed as an additional module for the FrustratometeR package, highlights the role of local frustration dynamics in protein fold-switching and offers a robust tool to enhance our understanding of other proteins with significant conformational shifts.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425668/pdf/","citationCount":"0","resultStr":"{\"title\":\"A contact-based analysis of local energetic frustration dynamics identifies key residues enabling RfaH fold-switch.\",\"authors\":\"Jorge González-Higueras, María Inés Freiberger, Pablo Galaz-Davison, R Gonzalo Parra, César A Ramírez-Sarmiento\",\"doi\":\"10.1002/pro.5182\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Fold-switching enables metamorphic proteins to reversibly interconvert between two highly dissimilar native states to regulate their protein functions. While about 100 proteins have been identified to undergo fold-switching, unveiling the key residues behind this mechanism for each protein remains challenging. Reasoning that fold-switching in proteins is driven by dynamic changes in local energetic frustration, we combined fold-switching simulations generated using simplified structure-based models with frustration analysis to identify key residues involved in this process based on the change in the density of minimally frustrated contacts during refolding. Using this approach to analyze the fold-switch of the bacterial transcription factor RfaH, we identified 20 residues that significantly change their frustration during its fold-switch, some of which have been experimentally and computationally reported in previous works. Our approach, which we developed as an additional module for the FrustratometeR package, highlights the role of local frustration dynamics in protein fold-switching and offers a robust tool to enhance our understanding of other proteins with significant conformational shifts.</p>\",\"PeriodicalId\":20761,\"journal\":{\"name\":\"Protein Science\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425668/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Protein Science\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1002/pro.5182\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Protein Science","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/pro.5182","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

折叠转换使变构蛋白质能够在两种高度不同的原生状态之间可逆地相互转换,从而调节其蛋白质功能。虽然已经发现约有 100 种蛋白质会发生折叠转换,但揭示每种蛋白质这一机制背后的关键残基仍然具有挑战性。我们认为蛋白质的折叠转换是由局部能量沮度的动态变化驱动的,因此我们将基于简化结构模型生成的折叠转换模拟与沮度分析相结合,根据重折叠过程中最小沮度接触密度的变化来确定参与这一过程的关键残基。利用这种方法分析细菌转录因子 RfaH 的折叠转换,我们发现了 20 个在折叠转换过程中沮度发生显著变化的残基,其中一些残基已在以前的工作中通过实验和计算得到了报告。我们的方法是作为 FrustratometeR 软件包的一个附加模块开发的,它强调了局部挫折动力学在蛋白质折叠转换中的作用,并为我们提供了一个强大的工具,以加深我们对其他具有显著构象转变的蛋白质的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A contact-based analysis of local energetic frustration dynamics identifies key residues enabling RfaH fold-switch.

Fold-switching enables metamorphic proteins to reversibly interconvert between two highly dissimilar native states to regulate their protein functions. While about 100 proteins have been identified to undergo fold-switching, unveiling the key residues behind this mechanism for each protein remains challenging. Reasoning that fold-switching in proteins is driven by dynamic changes in local energetic frustration, we combined fold-switching simulations generated using simplified structure-based models with frustration analysis to identify key residues involved in this process based on the change in the density of minimally frustrated contacts during refolding. Using this approach to analyze the fold-switch of the bacterial transcription factor RfaH, we identified 20 residues that significantly change their frustration during its fold-switch, some of which have been experimentally and computationally reported in previous works. Our approach, which we developed as an additional module for the FrustratometeR package, highlights the role of local frustration dynamics in protein fold-switching and offers a robust tool to enhance our understanding of other proteins with significant conformational shifts.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Protein Science
Protein Science 生物-生化与分子生物学
CiteScore
12.40
自引率
1.20%
发文量
246
审稿时长
1 months
期刊介绍: Protein Science, the flagship journal of The Protein Society, is a publication that focuses on advancing fundamental knowledge in the field of protein molecules. The journal welcomes original reports and review articles that contribute to our understanding of protein function, structure, folding, design, and evolution. Additionally, Protein Science encourages papers that explore the applications of protein science in various areas such as therapeutics, protein-based biomaterials, bionanotechnology, synthetic biology, and bioelectronics. The journal accepts manuscript submissions in any suitable format for review, with the requirement of converting the manuscript to journal-style format only upon acceptance for publication. Protein Science is indexed and abstracted in numerous databases, including the Agricultural & Environmental Science Database (ProQuest), Biological Science Database (ProQuest), CAS: Chemical Abstracts Service (ACS), Embase (Elsevier), Health & Medical Collection (ProQuest), Health Research Premium Collection (ProQuest), Materials Science & Engineering Database (ProQuest), MEDLINE/PubMed (NLM), Natural Science Collection (ProQuest), and SciTech Premium Collection (ProQuest).
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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