%0 Journal Article
%T Structural Analyses of a Constitutively Active Mutant of Exchange Protein Directly Activated by cAMP
%A Mark A. White
%A Sheng Li
%A Tamara Tsalkova
%A Fang C. Mei
%A Tong Liu
%A Virgil L. Woods
%A Xiaodong Cheng
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0049932
%X Exchange proteins directly activated by cAMP (EPACs) are important allosteric regulators of cAMP-mediated signal transduction pathways. To understand the molecular mechanism of EPAC activation, we have combined site-directed mutagenesis, X-ray crystallography, and peptide amide hydrogen/deuterium exchange mass spectrometry (DXMS) to probe the structural and conformational dynamics of EPAC2-F435G, a constitutively active EPAC2 mutant. Our study demonstrates that conformational dynamics plays a critical role in cAMP-induced EPAC activation. A glycine mutation at 435 position shifts the equilibrium of conformational dynamics towards the extended active conformation.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0049932