1m7e
From Proteopedia
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Crystal structure of the phosphotyrosine binding domain(PTB) of mouse Disabled 2(Dab2):implications for Reeling signaling
Overview
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.
About this Structure
1M7E is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
Crystal structures of the Dab homology domains of mouse disabled 1 and 2., Yun M, Keshvara L, Park CG, Zhang YM, Dickerson JB, Zheng J, Rock CO, Curran T, Park HW, J Biol Chem. 2003 Sep 19;278(38):36572-81. Epub 2003 Jun 24. PMID:12826668
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