Native state dynamics drive the unfolding of the SH3 domain of PI3 kinase at high denaturant concentration.

ABSTRACT: Little is known about the role of protein dynamics in directing protein unfolding along a specific pathway and about the role played by chemical denaturants in modulating the dynamics and the initiation of unfolding. In this study, deuterium-hydrogen exchange (HX) detected by electrospray ionization mass spectrometry (ESI-MS) was used to study the unfolding of the SH3 domain of the PI3 kinase. Unfolding on the principal unfolding pathway occurs in 2 steps, both in the absence and in the presence of 1.8 M guanidine hydrochloride (GdnHCl). In both cases, the first step leads to the formation of an intermediate, I(N), with 5 fewer protected amide hydrogen sites than in N. In the second step, I(N) loses the structure protecting the remaining 14 amide hydrogen sites from HX as it unfolds comple

SUBMITTER: Wani AH 

PROVIDER: S-EPMC2791584 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature