1OQN

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

Summary for 1OQN

• Entry DOI: 10.2210/pdb1oqn/pdb
• Descriptor: Disabled homolog 1, Alzheimer's disease amyloid A4 protein homolog, D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: ptb, inositol, app, signaling protein
• Biological source: Mus musculus (house mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P08592
• Total number of polymer chains: 4
• Total formula weight: 38933.97

Authors

Yun, M.,Keshvara, L.,Park, C.-G.,Zhang, Y.-M.,Dickerson, J.B.,Zheng, J.,Rock, C.O.,Curran, T.,Park, H.-W. (deposition date: 2003-03-10, release date: 2003-08-05, Last modification date: 2023-08-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.3 Å)