Distinct hydration properties of wild-type and familial point mutant A53T of α-synuclein associated with Parkinson's disease.

TitleDistinct hydration properties of wild-type and familial point mutant A53T of α-synuclein associated with Parkinson's disease.
Publication TypeJournal Article
Year of Publication2011
AuthorsHazy, E., M. Bokor, L. Kalmar, A. Gelencser, P. Kamasa, K-H. Han, K. Tompa, and P. Tompa
JournalBiophys J
Volume101
Issue9
Pagination2260-6
Date Published2011 Nov 2
ISSN1542-0086
Keywordsalpha-Synuclein, Amino Acid Substitution, Humans, Magnetic Resonance Spectroscopy, Molecular Dynamics Simulation, Mutant Proteins, Parkinson Disease, Point Mutation, Protein Structure, Tertiary, Temperature, Water
Abstract

The propensity of α-synuclein to form amyloid plays an important role in Parkinson's disease. Three familial mutations, A30P, E46K, and A53T, correlate with Parkinson's disease. Therefore, unraveling the structural effects of these mutations has basic implications in understanding the molecular basis of the disease. Here, we address this issue through comparing details of the hydration of wild-type α-synuclein and its A53T mutant by a combination of wide-line NMR, differential scanning calorimetry, and molecular dynamics simulations. All three approaches suggest a hydrate shell compatible with a largely disordered state of both proteins. Its fine details, however, are different, with the mutant displaying a somewhat higher level of hydration, suggesting a bias to more open structures, favorable for protein-protein interactions leading to amyloid formation. These differences disappear in the amyloid state, suggesting basically the same surface topology, irrespective of the initial monomeric state.

DOI10.1016/j.bpj.2011.08.052
Alternate JournalBiophys. J.
PubMed ID22067166
PubMed Central IDPMC3207174