Studying the interaction of Huntingtin and HAP40: potential functional implications

研究亨廷顿蛋白和 HAP40 的相互作用：潜在的功能意义

• 批准号: 412854449
• 负责人: Professor Dr. Stefan Kochanek
• 金额: --
• 依托单位: Abteilung Gentherapie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/412854449?language=en
• 关键词: Studying; interaction; Huntingtin; HAP40; potential

Huntington's disease (HD) is an inherited neurodegenerative disease that is caused by mutations in the Huntingtin (Htt) gene. Based on recombinant protein production in human cells we have recently determined the cryo-EM structure of the Huntingtin protein (HTT) with an abundant interaction partner, huntingtin-associated protein 40 (HAP40). Very little is known about the function of HAP40. Thus, the overall goal of this project is to gain increased scientific understanding of the meaning of the interaction of HAP40 with HTT and to obtain first insight into potential functions of HAP40.We will study the interaction of HTT and HAP40 at the phylogenetic level by performing bioinformatic studies and also by biochemically studying the interaction of HTT and HAP40 in non-human species. We will further identify interaction partners of HAP40 and of the HTT-HAP40 complex by proteomic analyses, since these interaction may inform on potential functions of the interaction between the proteins. Altogether, these studies will lead to an improved understanding of the functional meaning of the interaction of HTT and HAP40.

亨廷顿病（HD）是一种遗传性神经退行性疾病，由亨廷顿蛋白（Htt）基因突变引起。基于在人类细胞中的重组蛋白生产，我们最近确定了亨廷顿蛋白（HTT）的冷冻电镜结构与丰富的相互作用的合作伙伴，亨廷顿蛋白相关蛋白40（HAP 40）。关于HAP 40的功能知之甚少。因此，本项目的总体目标是加深对HAP 40与HTT相互作用意义的科学理解，并首次深入了解HAP 40的潜在功能。我们将通过生物信息学研究和非人类物种中HTT与HAP 40相互作用的生化研究，在系统发育水平上研究HTT与HAP 40的相互作用。我们将通过蛋白质组学分析进一步鉴定HAP 40和HTT-HAP 40复合物的相互作用伴侣，因为这些相互作用可能会告知蛋白质之间相互作用的潜在功能。总之，这些研究将导致HTT和HAP 40的相互作用的功能意义的更好的理解。