Work

Synchronous vs Asynchronous Chain Motion in α-Synuclein Contact Dynamics

Year: 2008

Type: article

Abstract: alpha-Synuclein (alpha-syn) is an intrinsically unstructured 140-residue neuronal protein of uncertain function that is implicated in the etiology of Parkinson's disease. Tertiary contact formation rate constants in alpha-syn, determined from diffusion-limited electron-transfer kinetics measurements, are poorly approximated by simple random polymer theory. One source of the discrepancy between theory and experiment may be that interior-loop formation rates are not well approximated by end-to-end contact dynamics models. We have addressed this issue with Monte Carlo simulations to model asynchronous and synchronous motion of contacting sites in a random polymer. These simulations suggest that a dynamical drag effect may slow interior-loop formation rates by about a factor of 2 in comparison to end-to-end loops of comparable size. The additional deviations from random coil behavior in alpha-syn likely arise from clustering of hydrophobic residues in the disordered polypeptide.

Source: The Journal of Physical Chemistry B

DOI: 10.1021/jp806727e

Authors: Kristopher G. Urie, David Angulo, Jennifer C. Lee, John J. Kozak, Harry B. Gray, Jay R. Winkler

Institutions: DePaul University, California Institute of Technology, National Institutes of Health, National Heart, Lung, and Blood Institute

Language: English

Topic: Protein Structure and Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases

Awards: G1974853788, Elucidating Protein Folding Mechanisms, Electron Transfer in Iron and Copper Oxygenases and Oxidases, G6110075961, G736126075