Title: Intermediates control domain swapping during folding of p13(suc1)
Authors: Rousseau, Frederic ×
Schymkowitz, Joost
Wilkinson, HR
Itzhaki, LS #
Issue Date: Feb-2004
Publisher: American Society for Biochemistry and Molecular Biology
Series Title: Journal of Biological Chemistry vol:279 issue:9 pages:8368-8377
Abstract: The 13-kDa protein p13(suc1) has two folded states, a monomer and a structurally similar domain-swapped dimer formed by exchange of a beta-strand. The refolding reaction of p13(suc1) is multiphasic, and in this paper we analyze the kinetics as a function of denaturant and protein concentration and compare the behavior of wild type and a set of mutants previously designed with dimerization propensities that span 9 orders of magnitude. We show that the folding reactions of wild type and all mutants produce the monomer predominantly despite their very different equilibrium behavior. However, the addition of low concentrations of denaturant in the refolding buffer leads to thermodynamic control of the folding reaction with products that correspond to the wild type and mutant equilibrium dimerization propensities. We present evidence that the kinetic control in the absence of urea arises because of the population of the folding intermediates. Intermediates are usually considered to be detrimental to folding because they slow down the reaction; however, our work shows that intermediates buffer the monomeric folding pathway against the effect of mutations that favor the nonfunctional, dimeric state at equilibrium.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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