Epac2, a guanine nucleotide exchange factor, regulates a wide variety of intracellular
processes in response to second messenger cAMP. In this study, we have used peptide
amide hydrogen/deuterium exchange mass spectrometry to probe the solution structural and
conformational dynamics of full-length Epac2 in the presence and absence of cAMP. The
results support a mechanism in which cAMP-induced Epac2 activation is mediated by a
major hinge motion centered on the C terminus of the second cAMP binding domain. This …