1MFL

The Structure of ERBIN PDZ domain bound to the Carboxy-terminal tail of the ErbB2 Receptor

1MFL の概要

• エントリーDOI: 10.2210/pdb1mfl/pdb
• 関連するPDBエントリー: 1MFG
• 分子名称: Erb-B2 INTERACTING PROTEIN, PHOSPHORYLATED Erb-B2 carboxyl-terminal fragment. (3 entities in total)
• 機能のキーワード: pdz domain, phosphorylation, erb-b2, erbin, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell junction, hemidesmosome : Q96RT1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 11376.71

構造登録者

Birrane, G.,Chung, J.,Ladias, J.A. (登録日: 2002-08-12, 公開日: 2003-01-21, 最終更新日: 2024-11-20)

主引用文献

Birrane, G.,Chung, J.,Ladias, J.A.
Novel mode of ligand recognition by the erbin PDZ domain
J.Biol.Chem., 278:1399-1402, 2003

PubMed Abstract: 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.

PubMed: 12444095
DOI: 10.1074/jbc.C200571200

実験手法

X-RAY DIFFRACTION (1.88 Å)