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1m7e

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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'''
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===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.
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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]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:43:37 2008''
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''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

Image:1m7e.png

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

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