Premium
Structure of an activated G protein‐coupled receptor kinase reveals its receptor‐docking domain
Author(s) -
Tesmer John JG,
Singh Puja,
Huang Chihchin
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.879.10
Subject(s) - g protein coupled receptor kinase , g protein coupled receptor , heterotrimeric g protein , microbiology and biotechnology , docking (animal) , receptor , chemistry , biology , biochemistry , biophysics , g protein , medicine , nursing
G protein‐coupled receptor (GPCR) kinases (GRKs) play a key role in the desensitization of GPCRs by phosphorylating the cytoplasmic loops and tails of activated receptors. How GRKs recognize and are in turn activated by these receptors is not understood. High resolution crystal structures have been determined for GRK1, GRK2, and GRK6, but in each of these structures the kinase domain assumes an open, inactive conformation, and key structural elements believed to be involved in the recognition of GPCRs are missing or poorly ordered. We have now determined the crystal structure of a GRK bound to a nucleotide substrate analog wherein the kinase domain assumes a closed, catalytically active conformation. In this structure, missing structural elements have coalesced to form a receptor‐docking domain that explains how receptor binding promotes kinase activation. Based on this structure we can model a GRK‐GPCR complex, leading us to propose that GRKs and heterotrimeric G proteins recognize activated receptors via similar mechanisms. Support for this research was provided by NIH grants HL071818 and HL086865.