2gs7: Difference between revisions

Revision as of 05:27, 4 May 2008

Crystal Structure of the inactive EGFR kinase domain in complex with AMP-PNP

OverviewOverview

The mechanism by which the epidermal growth factor receptor (EGFR) is activated upon dimerization has eluded definition. We find that the EGFR kinase domain can be activated by increasing its local concentration or by mutating a leucine (L834R) in the activation loop, the phosphorylation of which is not required for activation. This suggests that the kinase domain is intrinsically autoinhibited, and an intermolecular interaction promotes its activation. Using further mutational analysis and crystallography we demonstrate that the autoinhibited conformation of the EGFR kinase domain resembles that of Src and cyclin-dependent kinases (CDKs). EGFR activation results from the formation of an asymmetric dimer in which the C-terminal lobe of one kinase domain plays a role analogous to that of cyclin in activated CDK/cyclin complexes. The CDK/cyclin-like complex formed by two kinase domains thus explains the activation of EGFR-family receptors by homo- or heterodimerization.

About this StructureAbout this Structure

2GS7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor., Zhang X, Gureasko J, Shen K, Cole PA, Kuriyan J, Cell. 2006 Jun 16;125(6):1137-49. PMID:16777603 Page seeded by OCA on Sun May 4 05:27:33 2008

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OCA

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 [[Image:2gs7.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2gs7 |SIZE=350|CAPTION= <scene name='initialview01'>2gs7</scene>, resolution 2.600&Aring;
+The line below this paragraph, containing "STRUCTURE_2gs7", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= EGFR, ERBB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2gs7|  PDB=2gs7  |  SCENE=  }}
-|RELATEDENTRY=[[2gs2|2GS2]], [[2gs6|2GS6]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gs7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gs7 OCA], [http://www.ebi.ac.uk/pdbsum/2gs7 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2gs7 RCSB]</span>
-}}
 '''Crystal Structure of the inactive EGFR kinase domain in complex with AMP-PNP'''
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 [[Category: Shen, K.]]
 [[Category: Zhang, X.]]
-[[Category: amp-pnp]]
+[[Category: Amp-pnp]]
-[[Category: egfr]]
+[[Category: Egfr]]
-[[Category: inactive]]
+[[Category: Inactive]]
-[[Category: kinase]]
+[[Category: Kinase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 05:27:33 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:20:46 2008''