Molecular mechanisms of heterogeneous oligomerization of huntingtin proteins.

ABSTRACT: There is still no successful strategy to treat Huntington's disease, an inherited autosomal disorder associated with the aggregation of mutated forms of the huntingtin protein containing polyglutamine tracts with more than 36 repeats. Recent experimental evidence is challenging the conventional view of the disease by revealing transcellular transfer of mutated huntingtin proteins which are able to seed oligomers involving wild type forms of the protein. Here we decipher the molecular mechanism of this unconventional heterogeneous oligomerization by performing discrete molecular dynamics simulations. We identify the most probable oligomer conformations and the molecular regions that can be targeted to destabilize them. Our computational findings are complemented experimentally by fluorescen

SUBMITTER: Bonfanti S 

PROVIDER: S-EPMC6527588 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature