1O7F

CRYSTAL STRUCTURE OF THE REGULATORY DOMAIN OF EPAC2

Summary for 1O7F

• Entry DOI: 10.2210/pdb1o7f/pdb
• Descriptor: CAMP-DEPENDENT RAP1 GUANINE-NUCLEOTIDE EXCHANGE FACTOR (2 entities in total)
• Functional Keywords: epac2, camp-gef2, camp, campb binding doamin, gef, exchange factor, regulation
• Biological source: MUS MUSCULUS (MOUSE)
• Total number of polymer chains: 1
• Total formula weight: 53270.60

Authors

Rehmann, H.,Prakash, B.,Wolf, E.,Rueppel, A.,De Rooij, J.,Bos, J.L.,Wittinghofer, A. (deposition date: 2002-11-04, release date: 2002-11-11, Last modification date: 2024-05-08)

Primary citation

Rehmann, H.,Prakash, B.,Wolf, E.,Rueppel, A.,De Rooij, J.,Bos, J.L.,Wittinghofer, A.
Structure and Regulation of the Camp-Binding Domains of Epac2
Nat.Struct.Biol., 10:26-, 2002

PubMed Abstract: 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.

PubMed: 12469113
DOI: 10.1038/NSB878

Experimental method

X-RAY DIFFRACTION (2.5 Å)