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Literature DB >> 15643843

Mapping long-range interactions in alpha-synuclein using spin-label NMR and ensemble molecular dynamics simulations.

Matthew M Dedmon¹, Kresten Lindorff-Larsen, John Christodoulou, Michele Vendruscolo, Christopher M Dobson.

Abstract

The intrinsically disordered protein alpha-synuclein plays a key role in the pathogenesis of Parkinson's disease (PD). We show here that the native state of alpha-synuclein consists of a broad distribution of conformers with an ensemble-averaged hydrodynamic radius significantly smaller than that expected for a random coil structure. This partial condensation is driven by interactions between the highly charged C-terminus and a large hydrophobic central region of the protein sequence. We suggest that this structure could inhibit the formation of alpha-synuclein aggregates, which are thought to be the cytotoxic species responsible for neurodegeneration in PD.

Entities: Disease Gene

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Year: 2005 PMID： 15643843 DOI： 10.1021/ja044834j

Source DB: PubMed Journal: J Am Chem Soc ISSN： 0002-7863 Impact factor: 15.419

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Cited

248 in total

1. The N-terminus of the intrinsically disordered protein α-synuclein triggers membrane binding and helix folding.

Authors: Tim Bartels; Logan S Ahlstrom; Avigdor Leftin; Frits Kamp; Christian Haass; Michael F Brown; Klaus Beyer
Journal: Biophys J Date: 2010-10-06 Impact factor: 4.033

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

Authors: E Hazy; M Bokor; L Kalmar; A Gelencser; P Kamasa; K-H Han; K Tompa; P Tompa
Journal: Biophys J Date: 2011-11-01 Impact factor: 4.033

Mapping long-range interactions in alpha-synuclein using spin-label NMR and ensemble molecular dynamics simulations.

1. The N-terminus of the intrinsically disordered protein α-synuclein triggers membrane binding and helix folding.

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

3. Multiscale ensemble modeling of intrinsically disordered proteins: p53 N-terminal domain.

4. Chain collapse of an amyloidogenic intrinsically disordered protein.

5. Aggregation of α-synuclein is kinetically controlled by intramolecular diffusion.

Review 6. Dynamic structural flexibility of α-synuclein.

7. Transient β-hairpin formation in α-synuclein monomer revealed by coarse-grained molecular dynamics simulation.

8. Structural basis of the interplay between α-synuclein and Tau in regulating pathological amyloid aggregation.

9. Adsorption and decontamination of α-synuclein from medically and environmentally-relevant surfaces.

Review 10. In-Cell NMR Spectroscopy of Intrinsically Disordered Proteins.