1m7e
From Proteopedia
(New page: 200px<br /><applet load="1m7e" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m7e, resolution 2.45Å" /> '''Crystal structure of...) |
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| - | [[Image:1m7e.jpg|left|200px]]<br /><applet load="1m7e" size=" | + | [[Image:1m7e.jpg|left|200px]]<br /><applet load="1m7e" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1m7e, resolution 2.45Å" /> | caption="1m7e, resolution 2.45Å" /> | ||
'''Crystal structure of the phosphotyrosine binding domain(PTB) of mouse Disabled 2(Dab2):implications for Reeling signaling'''<br /> | '''Crystal structure of the phosphotyrosine binding domain(PTB) of mouse Disabled 2(Dab2):implications for Reeling signaling'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Disabled (Dab) 1 and 2 are mammalian homologues of Drosophila DAB. Dab1 is | + | 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== | ==About this Structure== | ||
| - | 1M7E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http:// | + | 1M7E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M7E OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Curran, T.]] | [[Category: Curran, T.]] | ||
| - | [[Category: Dickerson, J | + | [[Category: Dickerson, J B.]] |
[[Category: Keshvara, L.]] | [[Category: Keshvara, L.]] | ||
| - | [[Category: Park, C | + | [[Category: Park, C G.]] |
| - | [[Category: Park, H | + | [[Category: Park, H W.]] |
| - | [[Category: Rock, C | + | [[Category: Rock, C O.]] |
[[Category: Yun, M.]] | [[Category: Yun, M.]] | ||
| - | [[Category: Zhang, Y | + | [[Category: Zhang, Y M.]] |
[[Category: Zheng, J.]] | [[Category: Zheng, J.]] | ||
[[Category: protein-peptide complex]] | [[Category: protein-peptide complex]] | ||
[[Category: ptb]] | [[Category: ptb]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:52:19 2008'' |
Revision as of 11:52, 21 February 2008
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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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