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protein Protein-protein interface(s) links
Transferase PDB id
1ym7
Jmol
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    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P21146  (ARBK1_BOVIN) -  Beta-adrenergic receptor kinase 1
Seq:
Struc:
 
Seq:
Struc:
689 a.a.
608 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.15  - [Beta-adrenergic-receptor] kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + [beta-adrenergic receptor] = ADP + [beta-adrenergic receptor] phosphate
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 
  GO annot!
  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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19913059 A.W.Kahsai, S.Zhu, and G.Fenteany (2010).
G protein-coupled receptor kinase 2 activates radixin, regulating membrane protrusion and motility in epithelial cells.
  Biochim Biophys Acta, 1803, 300-310.  
20729810 C.A.Boguth, P.Singh, C.C.Huang, and J.J.Tesmer (2010).
Molecular basis for activation of G protein-coupled receptor kinases.
  EMBO J, 29, 3249-3259.
PDB codes: 3nyn 3nyo
20038610 F.Baameur, D.H.Morgan, H.Yao, T.M.Tran, R.A.Hammitt, S.Sabui, J.S.McMurray, O.Lichtarge, and R.B.Clark (2010).
Role for the regulator of G-protein signaling homology domain of G protein-coupled receptor kinases 5 and 6 in beta 2-adrenergic receptor and rhodopsin phosphorylation.
  Mol Pharmacol, 77, 405-415.  
20128603 J.J.Tesmer, V.M.Tesmer, D.T.Lodowski, H.Steinhagen, and J.Huber (2010).
Structure of human G protein-coupled receptor kinase 2 in complex with the kinase inhibitor balanol.
  J Med Chem, 53, 1867-1870.
PDB codes: 3krw 3krx
19364770 C.C.Huang, K.Yoshino-Koh, and J.J.Tesmer (2009).
A Surface of the Kinase Domain Critical for the Allosteric Activation of G Protein-coupled Receptor Kinases.
  J Biol Chem, 284, 17206-17215.  
19715378 C.S.Pao, B.L.Barker, and J.L.Benovic (2009).
Role of the amino terminus of G protein-coupled receptor kinase 2 in receptor phosphorylation.
  Biochemistry, 48, 7325-7333.  
19338266 R.Sterne-Marr, P.A.Leahey, J.E.Bresee, H.M.Dickson, W.Ho, M.J.Ragusa, R.M.Donnelly, S.M.Amie, J.A.Krywy, E.D.Brookins-Danz, S.C.Orakwue, M.J.Carr, K.Yoshino-Koh, Q.Li, and J.J.Tesmer (2009).
GRK2 activation by receptors: role of the kinase large lobe and carboxyl-terminal tail.
  Biochemistry, 48, 4285-4293.  
18488142 A.V.Smrcka (2008).
G protein betagamma subunits: central mediators of G protein-coupled receptor signaling.
  Cell Mol Life Sci, 65, 2191-2214.  
18339619 P.Singh, B.Wang, T.Maeda, K.Palczewski, and J.J.Tesmer (2008).
Structures of rhodopsin kinase in different ligand states reveal key elements involved in G protein-coupled receptor kinase activation.
  J Biol Chem, 283, 14053-14062.
PDB codes: 3c4w 3c4x 3c4y 3c4z 3c50 3c51
17134719 Q.Li, M.R.Nance, R.Kulikauskas, K.Nyberg, R.Fehon, P.A.Karplus, A.Bretscher, and J.J.Tesmer (2007).
Self-masking in an intact ERM-merlin protein: an active role for the central alpha-helical domain.
  J Mol Biol, 365, 1446-1459.
PDB codes: 2i1j 2i1k
16613860 D.T.Lodowski, V.M.Tesmer, J.L.Benovic, and J.J.Tesmer (2006).
The structure of G protein-coupled receptor kinase (GRK)-6 defines a second lineage of GRKs.
  J Biol Chem, 281, 16785-16793.
PDB code: 2acx
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.