%0 Journal Article %T Structural determinants of calmodulin binding to the intracellular C-terminal domain of the metabotropic glutamate receptor 7A. %+ Max Planck Institute for Brain Research %+ School of Biological Sciences %A Scheschonka, Astrid %A Findlow, Stuart %A Schemm, Rudolf %A El Far, Oussama %A Caldwell, John, H. %A Crump, Matthew, P. %A Holden-Dye, Kate %A O'Connor, Vincent %A Betz, Heinrich %A Werner, Jörn, M. %< avec comité de lecture %@ 0021-9258 %J Journal of Biological Chemistry %I American Society for Biochemistry and Molecular Biology %V 283 %N 9 %P 5577-88 %8 2008-02-29 %D 2008 %R 10.1074/jbc.M709505200 %M 18089570 %Z Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Journal articles %X Calmodulin (CaM) binds in a Ca2+-dependent manner to the intracellular C-terminal domains of most group III metabotropic glutamate receptors (mGluRs). Here we combined mutational and biophysical approaches to define the structural basis of CaM binding to mGluR 7A. Ca2+/CaM was found to interact with mGluR 7A primarily via its C-lobe at a 1:1 CaM:C-tail stoichiometry. Pulldown experiments with mutant CaM and mGluR 7A C-tail constructs and high resolution NMR with peptides corresponding to the CaM binding region of mGluR 7A allowed us to define hydrophobic and ionic interactions required for Ca2+/CaM binding and identified a 1-8-14 CaM-binding motif. The Ca2+/CaM.mGluR 7A peptide complex displays a classical wraparound structure that closely resembles that formed by Ca2+/CaM upon binding to smooth muscle myosin light chain kinase. Our data provide insight into how Ca2+/CaM regulates group III mGluR signaling via competition with intracellular proteins for receptor-binding sites. %G English %L inserm-00581220 %U https://inserm.hal.science/inserm-00581220 %~ INSERM