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| | {{STRUCTURE_1m7e| PDB=1m7e | SCENE= }} | | {{STRUCTURE_1m7e| PDB=1m7e | SCENE= }} |
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| - | '''Crystal structure of the phosphotyrosine binding domain(PTB) of mouse Disabled 2(Dab2):implications for Reeling signaling'''
| + | ===Crystal structure of the phosphotyrosine binding domain(PTB) of mouse Disabled 2(Dab2):implications for Reeling signaling=== |
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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: Protein-peptide complex]] | | [[Category: Protein-peptide complex]] |
| | [[Category: Ptb]] | | [[Category: Ptb]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:43:37 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 2 23:22:29 2008'' |
Revision as of 20:22, 2 July 2008
Template:STRUCTURE 1m7e
Crystal structure of the phosphotyrosine binding domain(PTB) of mouse Disabled 2(Dab2):implications for Reeling signaling
Template:ABSTRACT PUBMED 12826668
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
Page seeded by OCA on Wed Jul 2 23:22:29 2008
