1o7f
From Proteopedia
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CRYSTAL STRUCTURE OF THE REGULATORY DOMAIN OF EPAC2
Overview
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.
About this Structure
1O7F is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 14:14:24 2008
Categories: Mus musculus | Single protein | Bos, J L. | Prakash, B. | Rehmann, H. | Rooij, J De. | Rueppel, A. | Wittinghofer, A. | Wolf, E. | Camp | Camp-gef2 | Campb binding doamin | Epac2 | Exchange factor | Gef | Regulation
