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PLoS One. 2012;7(11):e49932. doi: 10.1371/journal.pone.0049932. Epub 2012 Nov 26.

Structural analyses of a constitutively active mutant of exchange protein directly activated by cAMP.

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1
Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch, Galveston, Texas, United States of America.

Abstract

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.

PMID:
23189173
PMCID:
PMC3506601
DOI:
10.1371/journal.pone.0049932
[Indexed for MEDLINE]
Free PMC Article
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