2byv
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STRUCTURE OF THE CAMP RESPONSIVE EXCHANGE FACTOR EPAC2 IN ITS AUTO-INHIBITED STATE
OverviewOverview
Epac proteins (exchange proteins directly activated by cAMP) are, guanine-nucleotide-exchange factors (GEFs) for the small GTP-binding, proteins Rap1 and Rap2 that are directly regulated by the second messenger, cyclic AMP and function in the control of diverse cellular processes, including cell adhesion and insulin secretion. Here we report the, three-dimensional structure of full-length Epac2, a 110-kDa protein that, contains an amino-terminal regulatory region with two, cyclic-nucleotide-binding domains and a carboxy-terminal catalytic region., The structure was solved in the absence of cAMP and shows the, auto-inhibited state of Epac. The regulatory region is positioned with, respect to the catalytic region by a rigid, tripartite beta-sheet-like, structure we refer to as the 'switchboard' and an ionic interaction we, call the 'ionic latch'. As a consequence of this arrangement, the access, of Rap to the catalytic site is sterically blocked. Mutational analysis, suggests a model for cAMP-induced Epac activation with rigid body movement, of the regulatory region, the features of which are universally conserved, in cAMP-regulated proteins.
About this StructureAbout this Structure
2BYV is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
Structure of the cyclic-AMP-responsive exchange factor Epac2 in its auto-inhibited state., Rehmann H, Das J, Knipscheer P, Wittinghofer A, Bos JL, Nature. 2006 Feb 2;439(7076):625-8. PMID:16452984
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