3qc9 | pdb_00003qc9

Crystal structure of cross-linked bovine GRK1 T8C/N480C double mutant complexed with ADP and Mg

spinqualitylabelsall models 3qc9, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3qc9 is a 4 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ADP, GOL, MG Gene: GRK1, RHOK (Bos taurus) Activity: Rhodopsin kinase, with EC number 2.7.11.14 Resources: FirstGlance, OCA, RCSB, PDBsum Function [RK_BOVIN] Retina-specific kinase involved in the signal turnoff via phosphorylation of rhodopsin (RHO), the G protein- coupled receptor that initiates the phototransduction cascade. This rapid desensitization is essential for scotopic vision and permits rapid adaptation to changes in illumination (By similarity). Publication Abstract from PubMed G protein-coupled receptor kinases (GRKs) phosphorylate activated G protein-coupled receptors (GPCRs) to initiate receptor desensitization. In addition to the canonical phosphoacceptor site of the kinase domain, activated receptors bind to a distinct docking site that confers higher affinity and activates GRKs allosterically. Recent mutagenesis and structural studies support a model wherein receptor docking activates a GRK by stabilizing the interaction of its ~20 amino acid N-terminal region with the kinase domain. This interaction in turn stabilizes a closed, more active conformation of the enzyme. To investigate the importance of this interaction for the process of GRK activation, we first validated the functionality of the N-terminal region in rhodopsin kinase (GRK1) by site-directed mutagenesis and then introduced a disulfide bond to cross-link the N-terminal region of GRK1 with its specific binding site on the kinase domain. Characterization of the kinetic and biophysical properties of the cross-linked protein showed that disulfide bond formation greatly enhances the catalytic efficiency of the peptide phosphorylation, but receptor-dependent phosphorylation, Meta II stabilization, and inhibition of transducin activation were unaffected. These data indicate that the interaction of the N-terminal region with the kinase domain is important for GRK activation, but that it does not dictate the affinity of GRKs for activated receptors. Activation of G protein-coupled receptor kinase 1 involves interactions between its N-terminal region and its kinase domain.,Huang CC, Orban T, Jastrzebska B, Palczewski K, Tesmer JJ Biochemistry. 2011 Jan 25. PMID:21265573 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Rhodopsin

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