Insights Into the Molecular Interactions of MIC2 and M2AP: Role of TSR6 and Conservation Across Species.

IF 3.2 4区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Proteins-Structure Function and Bioinformatics Pub Date : 2025-03-01 Epub Date: 2024-10-22 DOI:10.1002/prot.26758

Xu Xia, Chenqiang Du, Yang Wang, Gaojie Song

{"title":"Insights Into the Molecular Interactions of MIC2 and M2AP: Role of TSR6 and Conservation Across Species.","authors":"Xu Xia, Chenqiang Du, Yang Wang, Gaojie Song","doi":"10.1002/prot.26758","DOIUrl":null,"url":null,"abstract":"<p><p>Microneme protein 2 (MIC2) and its associated protein M2AP are pivotal for the gliding motility and host cell invasion by Toxoplasma gondii. In our prior work, we showed that M2AP binds specifically to the sixth TSR domain of MIC2, with this interaction mediated dominantly by the hotspot residue H620 situated at the center of TSR6. To delve deeper into the functional significance of H620 and explore the dynamic behavior of Y602, we conducted molecular dynamic (MD) simulations of the Toxoplasma TSR6-M2AP complex, encompassing both wild-type and mutant forms. Our findings underscore the critical role of H620 within TSR6, particularly its hydrogen bond interaction with K72 of M2AP. The H620A mutation disrupts the nearby hydrophobic network while minimally affecting other hydrophilic interactions. Furthermore, our data reveal a highly conserved binding pose between M2AP and TSR6 across different species, consistent with previous trans-genera studies, thereby offering insights for future strategies in infection control development.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"620-628"},"PeriodicalIF":3.2000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proteins-Structure Function and Bioinformatics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/prot.26758","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/22 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Microneme protein 2 (MIC2) and its associated protein M2AP are pivotal for the gliding motility and host cell invasion by Toxoplasma gondii. In our prior work, we showed that M2AP binds specifically to the sixth TSR domain of MIC2, with this interaction mediated dominantly by the hotspot residue H620 situated at the center of TSR6. To delve deeper into the functional significance of H620 and explore the dynamic behavior of Y602, we conducted molecular dynamic (MD) simulations of the Toxoplasma TSR6-M2AP complex, encompassing both wild-type and mutant forms. Our findings underscore the critical role of H620 within TSR6, particularly its hydrogen bond interaction with K72 of M2AP. The H620A mutation disrupts the nearby hydrophobic network while minimally affecting other hydrophilic interactions. Furthermore, our data reveal a highly conserved binding pose between M2AP and TSR6 across different species, consistent with previous trans-genera studies, thereby offering insights for future strategies in infection control development.

查看原文本刊更多论文

洞察 MIC2 和 M2AP 的分子相互作用：TSR6 的作用和跨物种保护

小体蛋白2（MIC2）及其相关蛋白M2AP对弓形虫的滑翔运动和宿主细胞侵袭至关重要。在之前的研究中，我们发现 M2AP 与 MIC2 的第六个 TSR 结构域特异性结合，这种相互作用主要由位于 TSR6 中心的热点残基 H620 介导。为了深入研究 H620 的功能意义并探索 Y602 的动态行为，我们对弓形虫 TSR6-M2AP 复合物（包括野生型和突变型）进行了分子动力学（MD）模拟。我们的发现强调了 H620 在 TSR6 中的关键作用，尤其是它与 M2AP 的 K72 之间的氢键相互作用。H620A 突变破坏了附近的疏水网络，而对其他亲水相互作用的影响却很小。此外，我们的数据揭示了不同物种中 M2AP 与 TSR6 之间高度保守的结合姿势，这与之前的跨种研究一致，从而为未来感染控制策略的开发提供了启示。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Proteins-Structure Function and Bioinformatics 生物-生化与分子生物学

CiteScore

5.90

自引率

3.40%

发文量

172

审稿时长

3 months

期刊介绍： PROTEINS : Structure, Function, and Bioinformatics publishes original reports of significant experimental and analytic research in all areas of protein research: structure, function, computation, genetics, and design. The journal encourages reports that present new experimental or computational approaches for interpreting and understanding data from biophysical chemistry, structural studies of proteins and macromolecular assemblies, alterations of protein structure and function engineered through techniques of molecular biology and genetics, functional analyses under physiologic conditions, as well as the interactions of proteins with receptors, nucleic acids, or other specific ligands or substrates. Research in protein and peptide biochemistry directed toward synthesizing or characterizing molecules that simulate aspects of the activity of proteins, or that act as inhibitors of protein function, is also within the scope of PROTEINS. In addition to full-length reports, short communications (usually not more than 4 printed pages) and prediction reports are welcome. Reviews are typically by invitation; authors are encouraged to submit proposed topics for consideration.