1mfg
From Proteopedia
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| , resolution 1.25Å | |||||||
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| Related: | 1FML
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
The Structure of ERBIN PDZ domain bound to the Carboxy-terminal tail of the ErbB2 Receptor
Overview
Erbin contains a class I PDZ domain that binds to the C-terminal region of the receptor tyrosine kinase ErbB2, a class II ligand. The crystal structure of the human Erbin PDZ bound to the peptide EYLGLDVPV corresponding to the C-terminal residues 1247-1255 of human ErbB2 has been determined at 1.25-A resolution. The Erbin PDZ deviates from the canonical PDZ fold in that it contains a single alpha-helix. The isopropyl group of valine at position -2 of the ErbB2 peptide interacts with the Erbin Val(1351) and displaces the peptide backbone away from the alpha-helix, elucidating the molecular basis of class II ligand recognition by a class I PDZ domain. Strikingly, the phenolic ring of tyrosine -7 enters into a pocket formed by the extended beta 2-beta 3 loop of the Erbin PDZ. Phosphorylation of tyrosine -7 abolishes this interaction but does not affect the binding of the four C-terminal peptidic residues to PDZ, as revealed by the crystal structure of the Erbin PDZ complexed with a phosphotyrosine-containing ErbB2 peptide. Since phosphorylation of tyrosine -7 plays a critical role in ErbB2 function, the selective binding and sequestration of this residue in its unphosphorylated state by the Erbin PDZ provides a novel mechanism for regulation of the ErbB2-mediated signaling and oncogenicity.
About this Structure
1MFG is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Novel mode of ligand recognition by the Erbin PDZ domain., Birrane G, Chung J, Ladias JA, J Biol Chem. 2003 Jan 17;278(3):1399-402. Epub 2002 Nov 19. PMID:12444095
Page seeded by OCA on Sun Mar 30 22:15:27 2008
