Studying the interaction of Huntingtin and HAP40: potential functional implications

亨廷顿病(HD)是一种遗传性神经退行性疾病，由亨廷顿(Htt)基因突变引起。基于在人类细胞中生产的重组蛋白，我们最近确定了Huntingtin蛋白(HTT)与丰富的相互作用伙伴Huntingtin相关蛋白40(HAP40)的低温EM结构。人们对HAP40的功能知之甚少。因此，本项目的总体目标是加深对HAP40和HAP40相互作用的意义的科学理解，并初步了解HAP40的潜在功能。我们将通过生物信息学研究和生物化学研究HTT和HAP40在非人类物种中的相互作用，在系统发育水平上研究HTT和HAP40的相互作用。我们将通过蛋白质组学分析进一步确定HAP40和HTT-HAP40复合体的相互作用伙伴，因为这些相互作用可能了解蛋白质之间相互作用的潜在功能。总之，这些研究将有助于更好地理解HTT和HAP40相互作用的功能意义。

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.