Effects of the Amyotrophic Lateral Sclerosis-related Q108P Mutation on the Structural Ensemble Characteristics of CHCHD10.

IF 1.9 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current protein & peptide science Pub Date : 2024-10-23 DOI:10.2174/0113892037335036241007043530

Hakan Alici, Vladimir N Uversky, David E Kang, Junga Alexa Woo, Orkid Coskuner-Weber

{"title":"Effects of the Amyotrophic Lateral Sclerosis-related Q108P Mutation on the Structural Ensemble Characteristics of CHCHD10.","authors":"Hakan Alici, Vladimir N Uversky, David E Kang, Junga Alexa Woo, Orkid Coskuner-Weber","doi":"10.2174/0113892037335036241007043530","DOIUrl":null,"url":null,"abstract":"Introduction: The Q108P pathological variant of the mitochondrial Coiled-Coil-Helix-- Coiled-Coil-Helix Domain-Containing Protein 10 (CHCHD10) has been implicated in amyotrophic lateral sclerosis (ALS). Both the wild-type and CHCHD10Q108P proteins exhibit intrinsically disordered regions, posing challenges for structural studies with conventional experimental tools.Method: This study presents the foundational characterization of the structural features of CHCHD10Q108P and compares them with those of the wild-type counterpart. We conducted multiple run molecular dynamics simulations and bioinformatics analyses.Result: Our findings reveal distinct differences in structural properties, free energy surfaces, and the outputs of principal component analysis between these two proteins. These results contribute significantly to the comprehension of CHCHD10 and its Q108P variant in terms of pathology, biochemistry, and structural biology.Conclusion: The reported structural properties hold promise for informing the development of more effective treatments for ALS.","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current protein & peptide science","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.2174/0113892037335036241007043530","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: The Q108P pathological variant of the mitochondrial Coiled-Coil-Helix-- Coiled-Coil-Helix Domain-Containing Protein 10 (CHCHD10) has been implicated in amyotrophic lateral sclerosis (ALS). Both the wild-type and CHCHD10Q108P proteins exhibit intrinsically disordered regions, posing challenges for structural studies with conventional experimental tools.

Method: This study presents the foundational characterization of the structural features of CHCHD10Q108P and compares them with those of the wild-type counterpart. We conducted multiple run molecular dynamics simulations and bioinformatics analyses.

Result: Our findings reveal distinct differences in structural properties, free energy surfaces, and the outputs of principal component analysis between these two proteins. These results contribute significantly to the comprehension of CHCHD10 and its Q108P variant in terms of pathology, biochemistry, and structural biology.

Conclusion: The reported structural properties hold promise for informing the development of more effective treatments for ALS.

查看原文本刊更多论文

肌萎缩侧索硬化症相关 Q108P 突变对 CHCHD10 结构组合特征的影响

简介线粒体Coil-Helix-Coil-Helix Domain-Containing Protein 10（CHCHD10）的Q108P病理变体与肌萎缩性脊髓侧索硬化症（ALS）有关。野生型蛋白和 CHCHD10Q108P 蛋白都表现出内在无序区，这给使用传统实验工具进行结构研究带来了挑战：本研究介绍了 CHCHD10Q108P 蛋白结构特征的基本特征，并将其与野生型蛋白的结构特征进行了比较。我们进行了多次分子动力学模拟和生物信息学分析：结果：我们的发现揭示了这两种蛋白质在结构特性、自由能面和主成分分析结果方面的明显差异。这些结果大大有助于从病理学、生物化学和结构生物学角度理解 CHCHD10 及其 Q108P 变体：结论：所报告的结构特性有望为开发更有效的 ALS 治疗方法提供信息。

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

Current protein & peptide science 生物-生化与分子生物学

CiteScore

5.20

自引率

0.00%

发文量

审稿时长

6 months

期刊介绍： Current Protein & Peptide Science publishes full-length/mini review articles on specific aspects involving proteins, peptides, and interactions between the enzymes, the binding interactions of hormones and their receptors; the properties of transcription factors and other molecules that regulate gene expression; the reactions leading to the immune response; the process of signal transduction; the structure and function of proteins involved in the cytoskeleton and molecular motors; the properties of membrane channels and transporters; and the generation and storage of metabolic energy. In addition, reviews of experimental studies of protein folding and design are given special emphasis. Manuscripts submitted to Current Protein and Peptide Science should cover a field by discussing research from the leading laboratories in a field and should pose questions for future studies. Original papers, research articles and letter articles/short communications are not considered for publication in Current Protein & Peptide Science.