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Structural determinants of calmodulin binding to the intracellular C-terminal domain of the metabotropic glutamate receptor 7A.

Abstract : 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.
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https://www.hal.inserm.fr/inserm-00581220
Contributor : Oussama El Far <>
Submitted on : Wednesday, March 30, 2011 - 2:41:03 PM
Last modification on : Saturday, June 8, 2019 - 2:20:03 PM

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Astrid Scheschonka, Stuart Findlow, Rudolf Schemm, Oussama El Far, John Caldwell, et al.. Structural determinants of calmodulin binding to the intracellular C-terminal domain of the metabotropic glutamate receptor 7A.. Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2008, 283 (9), pp.5577-88. ⟨10.1074/jbc.M709505200⟩. ⟨inserm-00581220⟩

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