Detection of transient interchain interactions in the intrinsically disordered protein alpha-synuclein by NMR paramagnetic relaxation enhancement - PubMed (original) (raw)

Detection of transient interchain interactions in the intrinsically disordered protein alpha-synuclein by NMR paramagnetic relaxation enhancement

Kuen-Phon Wu et al. J Am Chem Soc. 2010.

Abstract

NMR paramagnetic relaxation enhancement experiments were applied to the intrinsically disordered protein alpha-synuclein, the primary protein in Parkinson's disease, to directly characterize transient intermolecular complexes at neutral and low pH. At neutral pH, we observed weak N- to C-terminal interchain contacts driven by electrostatic interactions, while at low pH, the C- to C-terminal interchain interactions are significantly stronger and driven by hydrophobic contacts. Characterization of these first interchain interactions will provide fundamental insight into the mechanism of amyloid formation.

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Figures

Figure 1

Figure 1

Transient encounter complexes in the intrinsically disordered protein αSyn. The distribution of positively and negatively charged residues is shown with blue and red bars respectively (a). Inter-chain NMR PRE profiles for intrinsically disordered αSyn at pH 6.0 (b) and pH 2.5 (c). 1H Γ2 values with MTSL labels at A19C, A90C and G132C are shown for both sets of conditions. Models that illustrate the inter-chain interactions observed from the PRE experiments at neutral (d) and low pH (e). Monomer conformations were selected from the REMD ensemble generated at neutral and low pH in ref. and are shown as electrostatic surface potentials. The surface potential was calculated by Delphi and the color gradient from red to blue indicates surface potential from −2 to 2 kT/e.

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