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Structure paper

TitleStructure of Epac2 in complex with a cyclic AMP analogue and RAP1B.
Journal, issue, pagesNature, Vol. 455, Issue 7209, Page 124-127, Year 2008
Publish dateSep 4, 2008
AuthorsHolger Rehmann / Ernesto Arias-Palomo / Michael A Hadders / Frank Schwede / Oscar Llorca / Johannes L Bos /
PubMed AbstractEpac 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 ...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.
External linksNature / PubMed:18660803
MethodsEM (single particle) / X-ray diffraction
Resolution2.2 - 23.0 Å
Structure data

EMDB-1510:
Structure of full-length Epac2 in complex with cyclic-AMP and Rap.
Method: EM (single particle) / Resolution: 23.0 Å

PDB-3cf6:
Structure of Epac2 in complex with cyclic-AMP and Rap
Method: X-RAY DIFFRACTION / Resolution: 2.2 Å

Chemicals

ChemComp-SP1:
6-(6-AMINO-PURIN-9-YL)-2-THIOXO-TETRAHYDRO-2-FURO[3,2-D][1,3,2]DIOXAPHOSPHININE-2,7-DIOL

ChemComp-SO4:
SULFATE ION / Sulfate

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
  • synthetic construct (others)
KeywordsSIGNALING PROTEIN/GTP-BINDING PROTEIN / 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

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