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

Astrid Scheschonka 1 Stuart Findlow 2 Rudolf Schemm 1 Oussama El Far 1 John Caldwell 1 Matthew Crump 2 Kate Holden-Dye 2 Vincent O'Connor 2 Heinrich Betz 1, * Jörn Werner 2, *
* Auteur correspondant
1 Max Planck Institute for Brain Research
2 School of Biological Sciences
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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Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2008, 283 (9), pp.5577-88. 〈10.1074/jbc.M709505200〉
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Contributeur : Oussama El Far <>
Soumis le : mercredi 30 mars 2011 - 14:41:03
Dernière modification le : mercredi 29 août 2018 - 18:04:02

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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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