3CF6

Structure of Epac2 in complex with cyclic-AMP and Rap

Summary for 3CF6

• Entry DOI: 10.2210/pdb3cf6/pdb
• Related: 2BYV
• Descriptor: Rap guanine nucleotide exchange factor (GEF) 4, Ras-related protein Rap-1b, 6-(6-AMINO-PURIN-9-YL)-2-THIOXO-TETRAHYDRO-2-FURO[3,2-D][1,3,2]DIOXAPHOSPHININE-2,7-DIOL, ... (5 entities in total)
• Functional Keywords: epac, rapgef4, rap, rap1b, camp, sp-camps, gef, gunanine nucleotide exchange factor, g-protein, gtp-binding, nucleotide-binding, signaling protein regulator-gtp-binding protein complex, signaling protein-gtp-binding protein complex, signaling protein/gtp-binding protein
• Biological source: Mus musculus (mouse); More
• Cellular location: Cell membrane: P61224
• Total number of polymer chains: 2
• Total formula weight: 99084.95

Authors

Rehmann, H.,Arias-Palomo, E.,Hadders, M.A.,Schwede, F.,Llorca, O.,Bos, J.L. (deposition date: 2008-03-02, release date: 2008-07-29, Last modification date: 2023-11-01)

Primary citation

Rehmann, H.,Arias-Palomo, E.,Hadders, M.A.,Schwede, F.,Llorca, O.,Bos, J.L.
Structure of Epac2 in complex with a cyclic AMP analogue and RAP1B
Nature, 455:124-127, 2008

PubMed Abstract: Epac proteins are activated by binding of the second messenger cAMP and then act as guanine nucleotide exchange factors for Rap proteins. The Epac proteins are involved in the regulation of cell adhesion and insulin secretion. Here we have determined the structure of Epac2 in complex with a cAMP analogue (Sp-cAMPS) and RAP1B by X-ray crystallography and single particle electron microscopy. The structure represents the cAMP activated state of the Epac2 protein with the RAP1B protein trapped in the course of the exchange reaction. Comparison with the inactive conformation reveals that cAMP binding causes conformational changes that allow the cyclic nucleotide binding domain to swing from a position blocking the Rap binding site towards a docking site at the Ras exchange motif domain.

PubMed: 18660803
DOI: 10.1038/nature07187

Experimental method

X-RAY DIFFRACTION (2.2 Å)