HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 9, 5577-5588, February 29, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/9/5577    most recent M709505200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Scheschonka, A. Articles by Werner, J. M. PubMed PubMed Citation Articles by Scheschonka, A. Articles by Werner, J. M. Social Bookmarking                      What's this?

Structural Determinants of Calmodulin Binding to the Intracellular C-terminal Domain of the Metabotropic Glutamate Receptor 7A^*

Astrid Scheschonka, Stuart Findlow, Rudolf Schemm¹, Oussama El Far², John H. Caldwell³, Matthew P. Crump⁴, Kate Holden-Dye, Vincent O'Connor, Heinrich Betz⁵, and Jörn M. Werner⁶

From the Department of Neurochemistry, Max Planck Institute for Brain Research, 60528 Frankfurt, Germany and the School of Biological Sciences, University of Southampton, Southampton S016 7PX, United Kingdom

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.

Received for publication, November 20, 2007

^* This work was supported by the Max Planck Society (to H. B.), European Community Grant QLG3-CT-2001-00929 (to H. B. and V. O'C.), Fonds der Chemischen Industrie (to H. B.), and the Wessex Medical Trust (to V. O'C.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2.

¹ Present address: Max Planck Institute of Biophysical Chemistry, 37077 Göttingen, Germany.

² Present address: INSERM Unité 641, Université delaMéditerranée, Institut Jean Roche, FacultédeMédicine Secteur Nord, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France.

³ Present address: Dept. of Cellular and Developmental Biology, University of Colorado Health Sciences Center, Denver, CO 80045.

⁴ Present address: Dept. of Chemistry, University of Bristol, Cantocks Close, BS8 1TS Bristol, UK.

⁵ To whom correspondence may be addressed: Dept. of Neurochemistry, MPI for Brain Research, Deutschordenstrasse 46, 60528 Frankfurt, Germany. Tel.: 49-69-96769-220; Fax: 49-69-96769-441; E-mail: neurochemie{at}mpih-frankfurt.mpg.de. ⁶ To whom correspondence may be addressed: School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton S016 7PX, UK. Tel.: 44-2380592484; Fax: 44-2380594459; E-mail: jmwe{at}soton.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?