1f1w: Difference between revisions

Revision as of 15:47, 2 May 2008

SRC SH2 THREF1TRP MUTANT COMPLEXED WITH THE PHOSPHOPEPTIDE S(PTR)VNVQN

OverviewOverview

The Src SH2 domain binds pYEEI-containing phosphopeptides in an extended conformation with a hydrophobic pocket, which includes ThrEF1, binding Ile(pY +3). Mutating ThrEF1 to tryptophan switches specificity to an Asn(pY +2) requirement, yielding a biological mimic of the Grb2 SH2 domain. Here we show that the Src ThrEF1Trp SH2 domain mutant binds pYVNV phosphopeptides in a beta turn conformation, which, despite differing conformations of the interacting tryptophan, closely resembles the native Grb2/pYVNV cognate peptide binding mode. The ThrEF1Trp substitution therefore switches specificity by physically occluding the pTyr +3 binding pocket and by providing additional interaction surface area for Asn(pY +2). This demonstrates structurally how novel SH2 domain specificities may rapidly evolve through single amino acid substitutions and suggests how new signaling pathways may develop.

About this StructureAbout this Structure

1F1W is a Single protein structure of sequence from Gallus gallus. Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for specificity switching of the Src SH2 domain., Kimber MS, Nachman J, Cunningham AM, Gish GD, Pawson T, Pai EF, Mol Cell. 2000 Jun;5(6):1043-9. PMID:10911998 Page seeded by OCA on Fri May 2 15:47:19 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:1f1w.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1f1w |SIZE=350|CAPTION= <scene name='initialview01'>1f1w</scene>, resolution 2.10&Aring;
+The line below this paragraph, containing "STRUCTURE_1f1w", 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=PTR:O-PHOSPHOTYROSINE'>PTR</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/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1f1w|  PDB=1f1w  |  SCENE=  }}
-|RELATEDENTRY=[[1f2f|1F2F]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1f1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1f1w OCA], [http://www.ebi.ac.uk/pdbsum/1f1w PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1f1w RCSB]</span>
-}}
 '''SRC SH2 THREF1TRP MUTANT COMPLEXED WITH THE PHOSPHOPEPTIDE S(PTR)VNVQN'''
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 [[Category: Pai, E F.]]
 [[Category: Pawson, T.]]
-[[Category: phosphopeptide]]
+[[Category: Phosphopeptide]]
-[[Category: sh2 domain]]
+[[Category: Sh2 domain]]
-[[Category: specificity switch]]
+[[Category: Specificity switch]]
-[[Category: src]]
+[[Category: Src]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 15:47:19 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:14:05 2008''