Emerging β-Sheet Rich Conformations in Supercompact Huntingtin Exon-1 Mutant Structures.

ABSTRACT: There exists strong correlation between the extended polyglutamines (polyQ) within exon-1 of Huntingtin protein (Htt) and age onset of Huntington's disease (HD); however, the underlying molecular mechanism is still poorly understood. Here we apply extensive molecular dynamics simulations to study the folding of Htt-exon-1 across five different polyQ-lengths. We find an increase in secondary structure motifs at longer Q-lengths, including β-sheet content that seems to contribute to the formation of increasingly compact structures. More strikingly, these longer Q-lengths adopt supercompact structures as evidenced by a surprisingly small power-law scaling exponent (0.22) between the radius-of-gyration and Q-length that is substantially below expected values for compact globule structures (∼0.

SUBMITTER: Kang H 

PROVIDER: S-EPMC5835228 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature