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

E. Hazy, M. Bokor, L. Kalmár, A. Gelencser, P. Kamasa, K. H. Han, K. Tompa, P. Tompa

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18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2260-2266
Number of pages7
JournalBiophysical Journal
Volume101
Issue number9
DOIs
Publication statusPublished - 2011

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Synucleins
Amyloid
Parkinson Disease
Mutation
Proteins
Differential Scanning Calorimetry
Molecular Dynamics Simulation

ASJC Scopus subject areas

  • Biophysics

Cite this

Distinct hydration properties of wild-type and familial point mutant A53T of α-synuclein associated with Parkinson's disease. / Hazy, E.; Bokor, M.; Kalmár, L.; Gelencser, A.; Kamasa, P.; Han, K. H.; Tompa, K.; Tompa, P.

In: Biophysical Journal, Vol. 101, No. 9, 2011, p. 2260-2266.

Research output: Contribution to journalArticle

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