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Publication Abstract from PubMed

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.

Structural analyses of a constitutively active mutant of exchange protein directly activated by cAMP.,White MA, Li S, Tsalkova T, Mei FC, Liu T, Woods VL Jr, Cheng X PLoS One. 2012;7(11):e49932. doi: 10.1371/journal.pone.0049932. Epub 2012 Nov 26. PMID:23189173^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.