1f2f

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{{STRUCTURE_1f2f| PDB=1f2f | SCENE= }}
{{STRUCTURE_1f2f| PDB=1f2f | SCENE= }}
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'''SRC SH2 THREF1TRP MUTANT'''
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===SRC SH2 THREF1TRP MUTANT===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_10911998}}
==About this Structure==
==About this Structure==
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[[Category: Specificity switch]]
[[Category: Specificity switch]]
[[Category: Src]]
[[Category: Src]]
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Revision as of 23:23, 30 June 2008

Template:STRUCTURE 1f2f

SRC SH2 THREF1TRP MUTANT

Template:ABSTRACT PUBMED 10911998

About this Structure

1F2F is a Single protein structure of sequence from Gallus gallus. Full crystallographic information is available from OCA.

Reference

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

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