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Structure of Epac2 in complex with a cyclic AMP analogue and RAP1B.
- Source :
-
Nature [Nature] 2008 Sep 04; Vol. 455 (7209), pp. 124-7. Date of Electronic Publication: 2008 Jul 27. - Publication Year :
- 2008
-
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.
- Subjects :
- Amino Acid Motifs
Animals
Binding Sites
Carrier Proteins ultrastructure
Crystallography, X-Ray
Cyclic AMP chemistry
Cyclic AMP metabolism
Enzyme Activation
Guanine Nucleotide Exchange Factors ultrastructure
Humans
Mice
Microscopy, Electron
Models, Molecular
Protein Binding
Protein Conformation
rap GTP-Binding Proteins chemistry
rap GTP-Binding Proteins ultrastructure
Carrier Proteins chemistry
Carrier Proteins metabolism
Cyclic AMP analogs & derivatives
Guanine Nucleotide Exchange Factors chemistry
Guanine Nucleotide Exchange Factors metabolism
Thionucleotides chemistry
Thionucleotides metabolism
rap GTP-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 455
- Issue :
- 7209
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 18660803
- Full Text :
- https://doi.org/10.1038/nature07187