The predicted structure of the headpiece of the Huntingtin protein and its implications on Huntingtin aggregation.

ABSTRACT: We have performed simulated tempering molecular dynamics simulations to study the thermodynamics of the headpiece of the Huntingtin (Htt) protein (N17(Htt)). With converged sampling, we found this peptide is highly helical, as previously proposed. Interestingly, this peptide is also found to adopt two different and seemingly stable states. The region from residue 4 (L) to residue 9 (K) has a strong helicity from our simulations, which is supported by experimental studies. However, contrary to what was initially proposed, we have found that simulations predict the most populated state as a two-helix bundle rather than a single straight helix, although a significant percentage of structures do still adopt a single linear helix. The fact that Htt aggregation is nucleation dependent infers the

SUBMITTER: Kelley NW 

PROVIDER: S-EPMC2677131 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature