Transient interdomain interactions modulate the monomeric structural ensemble and self-assembly of Huntingtin Exon 1.

ABSTRACT: Polyglutamine expansion (≥ 36 residues) within the N-terminal exon-1 of Huntingtin (Httex1) leads to Huntington's disease, a neurodegenerative condition marked by the presence of intranuclear Htt inclusions. Notably, the polyglutamine tract in Httex1 is flanked by an N-terminal coiled-coil domain - N17 (17 amino acids), which undergoes self-association to promote the formation of soluble Httex1 oligomers and brings the aggregation-prone polyQ tracts in close spatial proximity. However, the mechanisms underlying the subsequent conversion of soluble oligomers into insoluble β-rich aggregates with increasing polyQ length, remain unclear. Current knowledge suggests that expansion of the polyQ tract increases its helicity, and this favors its oligomerization and aggregation. In addition, studie

SUBMITTER: Mohanty P 

PROVIDER: S-EPMC11100600 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature