1o7f: Difference between revisions
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{{STRUCTURE_1o7f| PDB=1o7f | SCENE= }} | |||
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'''CRYSTAL STRUCTURE OF THE REGULATORY DOMAIN OF EPAC2''' | '''CRYSTAL STRUCTURE OF THE REGULATORY DOMAIN OF EPAC2''' | ||
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[[Category: Wittinghofer, A.]] | [[Category: Wittinghofer, A.]] | ||
[[Category: Wolf, E.]] | [[Category: Wolf, E.]] | ||
[[Category: | [[Category: Camp]] | ||
[[Category: | [[Category: Camp-gef2]] | ||
[[Category: | [[Category: Campb binding doamin]] | ||
[[Category: | [[Category: Epac2]] | ||
[[Category: | [[Category: Exchange factor]] | ||
[[Category: | [[Category: Gef]] | ||
[[Category: | [[Category: Regulation]] | ||
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Revision as of 00:28, 3 May 2008
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 Sat May 3 03:28:46 2008