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| {{STRUCTURE_1p3r| PDB=1p3r | SCENE= }} | | {{STRUCTURE_1p3r| PDB=1p3r | SCENE= }} |
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| '''Crystal structure of the phosphotyrosin binding domain(PTB) of mouse Disabled 1(Dab1)'''
| | ===Crystal structure of the phosphotyrosin binding domain(PTB) of mouse Disabled 1(Dab1)=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_12826668}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 12826668 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_12826668}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Ptb]] | | [[Category: Ptb]] |
| [[Category: Signaling protein]] | | [[Category: Signaling protein]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:38:57 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 12:38:28 2008'' |
