1p3r: Difference between revisions
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New page: left|200px<br /><applet load="1p3r" size="450" color="white" frame="true" align="right" spinBox="true" caption="1p3r, resolution 2.1Å" /> '''Crystal structure of ... |
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[[Image:1p3r.gif|left|200px]]<br /><applet load="1p3r" size=" | [[Image:1p3r.gif|left|200px]]<br /><applet load="1p3r" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1p3r, resolution 2.1Å" /> | caption="1p3r, resolution 2.1Å" /> | ||
'''Crystal structure of the phosphotyrosin binding domain(PTB) of mouse Disabled 1(Dab1)'''<br /> | '''Crystal structure of the phosphotyrosin binding domain(PTB) of mouse Disabled 1(Dab1)'''<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== | ||
1P3R 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:// | 1P3R 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=1P3R 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: ptb]] | [[Category: ptb]] | ||
[[Category: signaling protein]] | [[Category: signaling protein]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:24:46 2008'' | ||
