1ym7: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1ym7.gif|left|200px]] | [[Image:1ym7.gif|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_1ym7", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
or leave the SCENE parameter empty for the default display. | |||
--> | |||
{{STRUCTURE_1ym7| PDB=1ym7 | SCENE= }} | |||
}} | |||
'''G Protein-Coupled Receptor Kinase 2 (GRK2)''' | '''G Protein-Coupled Receptor Kinase 2 (GRK2)''' | ||
| Line 25: | Line 22: | ||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Barnhill, J F.]] | [[Category: Barnhill, J F.]] | ||
[[Category: Ghirlando, R.]] | [[Category: Ghirlando, R.]] | ||
| Line 32: | Line 28: | ||
[[Category: Sterne-Marr, R.]] | [[Category: Sterne-Marr, R.]] | ||
[[Category: Tesmer, J J.G.]] | [[Category: Tesmer, J J.G.]] | ||
[[Category: | [[Category: Beta-ark1]] | ||
[[Category: | [[Category: G protein]] | ||
[[Category: | [[Category: Gpcr]] | ||
[[Category: | [[Category: Grk2]] | ||
[[Category: | [[Category: Kinase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:30:03 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 16:30, 3 May 2008
G Protein-Coupled Receptor Kinase 2 (GRK2)
OverviewOverview
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.
About this StructureAbout this Structure
1YM7 is a Single protein structure of sequence from Bos taurus. Full crystallographic information is available from OCA.
ReferenceReference
The role of G beta gamma and domain interfaces in the activation of G protein-coupled receptor kinase 2., Lodowski DT, Barnhill JF, Pyskadlo RM, Ghirlando R, Sterne-Marr R, Tesmer JJ, Biochemistry. 2005 May 10;44(18):6958-70. PMID:15865441 Page seeded by OCA on Sat May 3 16:30:03 2008