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Synchronous vs Asynchronous Chain Motion in α-Synuclein Contact Dynamics

Urie, Kristopher G. and Angulo, David and Lee, Jennifer C. and Kozak, John J. and Gray, Harry B. and Winkler, Jay R. (2009) Synchronous vs Asynchronous Chain Motion in α-Synuclein Contact Dynamics. Journal of Physical Chemistry B, 113 (2). pp. 522-530. ISSN 1520-6106. PMCID PMC2743092. http://resolver.caltech.edu/CaltechAUTHORS:URIjpcb09

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Abstract

α-Synuclein (α-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 α-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 α-syn likely arise from clustering of hydrophobic residues in the disordered polypeptide.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/jp806727eDOIArticle
http://pubs.acs.org/doi/abs/10.1021/jp806727ePublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743092PubMed CentralArticle
ORCID:
AuthorORCID
Winkler, Jay R.0000-0002-4453-9716
Additional Information:© 2008 American Chemical Society. Received: July 29, 2008; Revised Manuscript Received: October 10, 2008. Publication Date (Web): December 19, 2008. This research was supported by grants from the National Institutes of Health (GM068461 to J.R.W.; DK19038 to H.B.G.) and the Ellison Medical Foundation (Senior Scholar Award in Aging to H.B.G.), and by the Intramural Research Program of the National Institutes of Health, the National Heart, Lung, and Blood Institute (J.C.L.).
Funders:
Funding AgencyGrant Number
NIHGM068461
NIHDK19038
Ellison Medical FoundationUNSPECIFIED
National Heart, Lung, and Blood InstituteUNSPECIFIED
PubMed Central ID:PMC2743092
Record Number:CaltechAUTHORS:URIjpcb09
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:URIjpcb09
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:13192
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:02 Feb 2009 22:18
Last Modified:19 Sep 2017 17:42

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