Boguth, C. A., Singh, Puja, Huang, C. C., Tesmer, J. J. G. (August 2010) Molecular basis for activation of G protein-coupled receptor kinases. EMBO Journal, 29 (19). pp. 3249-3259.
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Abstract
G protein-coupled receptor (GPCR) kinases (GRKs) selectively recognize and are allosterically regulated by activated GPCRs, but the molecular basis for this interaction is not understood. Herein, we report crystal structures of GRK6 in which regions known to be critical for receptor phosphorylation have coalesced to stabilize the kinase domain in a closed state and to form a likely receptor docking site. The crux of this docking site is an extended N-terminal helix that bridges the large and small lobes of the kinase domain and lies adjacent to a basic surface of the protein proposed to bind anionic phospholipids. Mutation of exposed, hydrophobic residues in the N-terminal helix selectively inhibits receptor, but not peptide phosphorylation, suggesting that these residues interact directly with GPCRs. Our structural and biochemical results thus provide an explanation for how receptor recognition, phospholipid binding, and kinase activation are intimately coupled in GRKs. © 2010 European Molecular Biology Organization | All Rights Reserved.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | crystallography G protein-coupled receptors protein kinases regulation signal transduction |
| Subjects: | Investigative techniques and equipment > X-Ray Diffraction bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression |
| CSHL Authors: | |
| Communities: | CSHL labs > Furukawa lab |
| Depositing User: | CSHL Librarian |
| Date: | 20 August 2010 |
| Date Deposited: | 27 Sep 2011 15:13 |
| Last Modified: | 28 Feb 2018 21:02 |
| PMCID: | PMC2957210 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/15360 |
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