1P3R

Crystal structure of the phosphotyrosin binding domain(PTB) of mouse Disabled 1(Dab1)

1P3R の概要

• エントリーDOI: 10.2210/pdb1p3r/pdb
• 分子名称: Disabled homolog 2 (2 entities in total)
• 機能のキーワード: ptb, signaling protein
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Cytoplasmic vesicle, clathrin-coated vesicle membrane: P98078
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 54127.89

構造登録者

Yun, M.,Keshvara, L.,Park, C.G.,Zhang, Y.M.,Dickerson, J.B.,Zheng, J.,Rock, C.O.,Curran, T.,Park, H.W. (登録日: 2003-04-18, 公開日: 2003-08-05, 最終更新日: 2023-08-16)

主引用文献

Yun, M.,Keshvara, L.,Park, C.G.,Zhang, Y.M.,Dickerson, J.B.,Zheng, J.,Rock, C.O.,Curran, T.,Park, H.W.
Crystal structures of the Dab homology domains of mouse disabled 1 and 2.
J.Biol.Chem., 278:36572-36581, 2003

PubMed Abstract: Disabled (Dab) 1 and 2 are mammalian homologues of Drosophila DAB. Dab1 is a key cytoplasmic mediator in Reelin signaling that controls cell positioning in the developing central nervous system, whereas Dab2 is an adapter protein that plays a role in endocytosis. DAB family proteins possess an amino-terminal DAB homology (DH) domain that is similar to the phosphotyrosine binding/phosphotyrosine interaction (PTB/PI) domain. We have solved the structures of the DH domains of Dab2 (Dab2-DH) and Dab1 (Dab1-DH) in three different ligand forms, ligand-free Dab2-DH, the binary complex of Dab2-DH with the Asn-Pro-X-Tyr (NPXY) peptide of amyloid precursor protein (APP), and the ternary complex of Dab1-DH with the APP peptide and inositol 1,4,5-trisphosphate (Ins-1,4,5-P3, the head group of phosphatidylinositol-4,5-diphosphate (PtdIns-4,5-P2)). The similarity of these structures suggests that the rigid Dab DH domain maintains two independent pockets for binding of the APP/lipoprotein receptors and phosphoinositides. Mutagenesis confirmed the structural determinants specific for the NPXY sequence and PtdIns-4,5-P2 binding. NMR spectroscopy confirmed that the DH domain binds to Ins-1,4,5-P3 independent of the NPXY peptides. These findings suggest that simultaneous interaction of the rigid DH domain with the NPXY sequence and PtdIns-4,5-P2 plays a role in the attachment of Dab proteins to the APP/lipoprotein receptors and phosphoinositide-rich membranes.

PubMed: 12826668
DOI: 10.1074/jbc.M304384200

実験手法

X-RAY DIFFRACTION (2.1 Å)