The Structure of ERBIN PDZ domain bound to the Carboxy-terminal tail of the ErbB2 Receptor
Publication Abstract from PubMed
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
[LAP2_HUMAN] Acts as an adapter for the receptor ERBB2, in epithelia. By binding the unphosphorylated 'Tyr-1248' of receptor ERBB2, it may contribute to stabilize this unphosphorylated state.
About this Structure
1mfl is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
- ↑ Borg JP, Marchetto S, Le Bivic A, Ollendorff V, Jaulin-Bastard F, Saito H, Fournier E, Adelaide J, Margolis B, Birnbaum D. ERBIN: a basolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor. Nat Cell Biol. 2000 Jul;2(7):407-14. PMID:10878805 doi:10.1038/35017038