1o7f

CRYSTAL STRUCTURE OF THE REGULATORY DOMAIN OF EPAC2

spinqualitylabelsall models 1o7f, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1o7f is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RPGF4_MOUSE Guanine nucleotide exchange factor (GEF) for RAP1A, RAP1B and RAP2A small GTPases that is activated by binding cAMP. Seems not to activate RAB3A. Involved in cAMP-dependent, PKA-independent exocytosis through interaction with RIMS2. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Cyclic adenosine monophosphate (cAMP) is a universal second messenger that, in eukaryotes, was believed to act only on cAMP-dependent protein kinase A (PKA) and cyclic nucleotide-regulated ion channels. Recently, guanine nucleotide exchange factors specific for the small GTP-binding proteins Rap1 and Rap2 (Epacs) were described, which are also activated directly by cAMP. Here, we have determined the three-dimensional structure of the regulatory domain of Epac2, which consists of two cyclic nucleotide monophosphate (cNMP)-binding domains and one DEP (Dishevelled, Egl, Pleckstrin) domain. This is the first structure of a cNMP-binding domain in the absence of ligand, and comparison with previous structures, sequence alignment and biochemical experiments allow us to delineate a mechanism for cyclic nucleotide-mediated conformational change and activation that is most likely conserved for all cNMP-regulated proteins. We identify a hinge region that couples cAMP binding to a conformational change of the C-terminal regions. Mutations in the hinge of Epac can uncouple cAMP binding from its exchange activity. Structure and regulation of the cAMP-binding domains of Epac2.,Rehmann H, Prakash B, Wolf E, Rueppel A, de Rooij J, Bos JL, Wittinghofer A Nat Struct Biol. 2003 Jan;10(1):26-32. PMID:12469113 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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