PDBsum entry: 1ym7

Transferase

PDB id: 1ym7

Contents

Protein chains

608 a.a. *

* Residue conservation analysis

PDB id:

1ym7

Name:

Transferase

Title:

G protein-coupled receptor kinase 2 (grk2)

Structure:

Beta-adrenergic receptor kinase 1. Chain: a, b, c, d. Synonym: beta-ark-1, g- protein coupled receptor kinase 2. Engineered: yes. Mutation: yes

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Gene: adrbk1, grk2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.

Resolution:

4.50Å R-factor: 0.226 R-free: 0.279

Authors:

D.T.Lodowski,J.F.Barnhill,R.M.Pyskadlo,R.Ghirlando,R.Sterne- J.J.G.Tesmer

Key ref:

D.T.Lodowski et al. (2005). The role of G beta gamma and domain interfaces in the activation of G protein-coupled receptor kinase 2. Biochemistry, 44, 6958-6970. PubMed id: 15865441 DOI: 10.1021/bi050119q

Date:

20-Jan-05 Release date: 05-Jul-05

Protein chains

P21146  (ARBK1_BOVIN) -  Beta-adrenergic receptor kinase 1

Seq: 689 a.a.

Struc: 608 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.15 - [Beta-adrenergic-receptor] kinase.
• Reaction: ATP + [beta-adrenergic receptor] = ADP + [beta-adrenergic receptor] phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: intracellular (5 terms)
• Biological process: termination of G-protein coupled receptor signaling pathway (18 terms)
• Biochemical function: nucleotide binding (12 terms)

reference

DOI no: 10.1021/bi050119q

Biochemistry 44:6958-6970 (2005)

PubMed id: 15865441

The role of G beta gamma and domain interfaces in the activation of G protein-coupled receptor kinase 2.

D.T.Lodowski, J.F.Barnhill, R.M.Pyskadlo, R.Ghirlando, R.Sterne-Marr, J.J.Tesmer.

ABSTRACT

In response to extracellular signals, G protein-coupled receptors (GPCRs) catalyze guanine nucleotide exchange on Galpha subunits, enabling both activated Galpha and Gbetagamma subunits to target downstream effector enzymes. One target of Gbetagamma is G protein-coupled receptor kinase 2 (GRK2), an enzyme that initiates homologous desensitization by phosphorylating activated GPCRs. GRK2 consists of three distinct domains: an RGS homology (RH) domain, a protein kinase domain, and a pleckstrin homology (PH) domain, through which it binds Gbetagamma. The crystal structure of the GRK2-Gbetagamma complex revealed that the domains of GRK2 are intimately associated and left open the possibility for allosteric regulation by Gbetagamma. In this paper, we report the 4.5 A structure of GRK2, which shows that the binding of Gbetagamma does not induce large domain rearrangements in GRK2, although small rotations of the RH and PH domains relative to the kinase domain are evident. Mutation of residues within the larger domain interfaces of GRK2 generally leads to diminished expression and activity, suggesting that these interfaces are important for stability and remain intact upon activation of GRK2. Geranylgeranylated Gbetagamma, but not a soluble mutant of Gbetagamma, protects GRK2 from clostripain digestion at a site within its kinase domain that is 80 A away from the Gbetagamma binding site. Equilibrium ultracentrifugation experiments indicate that neither abnormally large detergent micelles nor protein oligomerization can account for the observed protection. The Gbetagamma-mediated binding of GRK2 to CHAPS micelles or lipid bilayers therefore appears to rigidify the kinase domain, perhaps by encouraging stable contacts between the RH and kinase domains.