Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 135, Issue 4, Pages 1415-1422Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ja309527h
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Funding
- Wellcome Trust [WT095195MA]
- BBSRC studentship
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Coupled folding and binding of intrinsically disordered proteins (IDPs) is prevalent in biology. As the first step toward understanding the mechanism of binding, it is important to know if a reaction is 'diffusion-limited' as, if this speed limit is reached, the association must proceed through an induced fit mechanism. Here, we use a model system where the 'BH3 region' of PUMA, an IDP, forms a single, contiguous alpha-helix upon binding the folded protein Mcl-1. Using stopped. flow techniques, we systematically compare the rate constant for association (k(+)) under a number of solvent conditions and temperatures. We show that our system is not 'diffusion-limited', despite having a k(+) in the often-quoted 'diffusion-limited' regime (10(5)-10(6) M-1 s(-1) at high ionic strength) and displaying an inverse dependence on solvent viscosity. These standard tests, developed for folded protein-protein interactions, are not appropriate for reactions where one protein is disordered.
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