Length-Dependent Structural Transformations of Huntingtin PolyQ Domain Upon Binding to 2D-Nanomaterials.

ABSTRACT: There is a strong negative correlation between the polyglutamine (polyQ) domain length (Q-length) in the intrinsically disordered Huntingtin protein (Htt) exon-1 and the age of onset of Huntington's disease (HD). PolyQ of Q-length longer than 40 has the propensity of forming very compact aggregate structures, leading to HD at full penetrance. Recent advances in nanobiotechnology provided a new platform for the development of novel diagnosis and therapeutics. Here, we explore the possibility of utilizing 2D-nanomaterials to inhibit the formation of supercompact polyQ structures through the so-called "folding-upon-binding" where the protein structure is dependent on the binding substrate. Using molecular dynamics simulations, we characterize two polyQ peptides with Q-length of 22 (Q22, norma

SUBMITTER: Feng M 

PROVIDER: S-EPMC7189795 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature