@article{e7c6825a15d84ea78dc5e8545ca7e3c5,
title = "Structure of Epac2 in complex with a cyclic AMP analogue and RAP1B",
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.",
author = "Holger Rehmann and Ernesto Arias-Palomo and Hadders, {Michael A.} and Frank Schwede and Oscar Llorca and Bos, {Johannes L.}",
note = "Funding Information: Acknowledgements We thank P. Gros for access to crystallization robots, M. Rensen-De Leeuw for technical assistance, A. Wittinghofer for reading the manuscript, the European Synchrotron Radiation Facility for providing synchrotron facilities, the scientists at ID23-1 for help with data collection, and the Galicia Supercomputer Centre (CESGA) and the Barcelona Supercomputing Centre for computing resources. H.R. is a recipient of the Hendrik Casimir-Karl Ziegler-Forschungspreis of the Nordrhein-Westf{\"a}lischen Akademie der Wissenschaften and the Koninklijke Nederlandse Akademie van Wetenschappen. E.A.-P. and O.L. are supported by the Autonomous Region of Madrid, F.S. by the Bremer Innovationsagentur, O.L. by the Spanish Ministry of Education and Science (MEC) and the Red Tem{\'a}tica de Investigaci{\'o}n cooperativa en C{\'a}ncer (RTICC), and J.L.B. by the Chemical Sciences and the Netherlands Genomic Initiative of the Netherlands Organisation for Scientific Research (NWO).",
year = "2008",
month = sep,
day = "4",
doi = "10.1038/nature07187",
language = "English (US)",
volume = "455",
pages = "124--127",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7209",
}