Electrostatic effects in filamentous protein aggregation. 


Author: Buell AK, Hung P, Salvatella X, Welland ME, Dobson CM, Knowles TP.

Affiliation: Department of Chemistry, University of Cambridge, Cambridge, United Kingdom. 
Conference/Journal: Biophys J.
Date published: 2013 Mar 5
Other:
 Volume ID: 104   ,  Issue ID: 5   ,  Pages: 1116-26   ,  Special Notes: doi: 10.1016/j.bpj.2013.01.031   ,  Word Count: 185  
    

Electrostatic forces play a key role in mediating interactions between proteins. However, gaining quantitative insights into the complex effects of electrostatics on protein behavior has proved challenging, due to the wide palette of scenarios through which both cations and anions can interact with polypeptide molecules in a specific manner or can result in screening in solution. In this article, we have used a variety of biophysical methods to probe the steady-state kinetics of fibrillar protein self-assembly in a highly quantitative manner to detect how it is modulated by changes in solution ionic strength. Due to the exponential modulation of the reaction rate by electrostatic forces, this reaction represents an exquisitely sensitive probe of these effects in protein-protein interactions. Our approach, which involves a combination of experimental kinetic measurements and theoretical analysis, reveals a hierarchy of electrostatic effects that control protein aggregation. Furthermore, our results provide a highly sensitive method for the estimation of the magnitude of binding of a variety of ions to protein molecules.

Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

PMID: 23473495 [PubMed - indexed for MEDLINE] PMCID: PMC3610013



keyword: proteomics