Studying the interaction of Huntingtin and HAP40: potential functional implications

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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.