2ci8: Difference between revisions
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==Overview== | ==Overview== | ||
Nck proteins are essential Src homology (SH) 2 and SH3 domain-bearing | Nck proteins are essential Src homology (SH) 2 and SH3 domain-bearing adapters that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. Two mammalian pathogens, enteropathogenic Escherichia coli and vaccinia virus, exploit Nck as part of their infection strategy. Conflicting data indicate potential differences in the recognition specificities of the SH2 domains of the isoproteins Nck1 (Nckalpha) and Nck2 (Nckbeta and Grb4). We have characterized the binding specificities of both SH2 domains and find them to be essentially indistinguishable. Crystal structures of both domains in complex with phosphopeptides derived from the enteropathogenic E. coli protein Tir concur in identifying highly conserved, specific recognition of the phosphopeptide. Differential peptide recognition can therefore not account for the preference of either Nck in particular signaling pathways. Binding studies using sequentially mutated, high affinity phosphopeptides establish the sequence variability tolerated in peptide recognition. Based on this binding motif, we identify potential new binding partners of Nck1 and Nck2 and confirm this experimentally for the Arf-GAP GIT1. | ||
==Disease== | ==Disease== | ||
Known | Known diseases associated with this structure: Skin/hair/eye pigmentation 6, blond/brown hair OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609840 609840]], Skin/hair/eye pigmentation 6, blue/green eyes OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609840 609840]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Findeis, A | [[Category: Findeis, A C.]] | ||
[[Category: Frese, S.]] | [[Category: Frese, S.]] | ||
[[Category: Heinz, D | [[Category: Heinz, D W.]] | ||
[[Category: Marquardt, T.]] | [[Category: Marquardt, T.]] | ||
[[Category: Roske, Y | [[Category: Roske, Y S.]] | ||
[[Category: Schubert, W | [[Category: Schubert, W D.]] | ||
[[Category: Stradal, T | [[Category: Stradal, T E.B.]] | ||
[[Category: 1PE]] | [[Category: 1PE]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
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[[Category: sh3 domain]] | [[Category: sh3 domain]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:48:54 2008'' | ||
Revision as of 17:48, 21 February 2008
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SH2 DOMAIN OF HUMAN NCK1 ADAPTOR PROTEIN- UNCOMPLEXED
OverviewOverview
Nck proteins are essential Src homology (SH) 2 and SH3 domain-bearing adapters that modulate actin cytoskeleton dynamics by linking proline-rich effector molecules to tyrosine kinases or phosphorylated signaling intermediates. Two mammalian pathogens, enteropathogenic Escherichia coli and vaccinia virus, exploit Nck as part of their infection strategy. Conflicting data indicate potential differences in the recognition specificities of the SH2 domains of the isoproteins Nck1 (Nckalpha) and Nck2 (Nckbeta and Grb4). We have characterized the binding specificities of both SH2 domains and find them to be essentially indistinguishable. Crystal structures of both domains in complex with phosphopeptides derived from the enteropathogenic E. coli protein Tir concur in identifying highly conserved, specific recognition of the phosphopeptide. Differential peptide recognition can therefore not account for the preference of either Nck in particular signaling pathways. Binding studies using sequentially mutated, high affinity phosphopeptides establish the sequence variability tolerated in peptide recognition. Based on this binding motif, we identify potential new binding partners of Nck1 and Nck2 and confirm this experimentally for the Arf-GAP GIT1.
DiseaseDisease
Known diseases associated with this structure: Skin/hair/eye pigmentation 6, blond/brown hair OMIM:[609840], Skin/hair/eye pigmentation 6, blue/green eyes OMIM:[609840]
About this StructureAbout this Structure
2CI8 is a Single protein structure of sequence from Homo sapiens with and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
The phosphotyrosine peptide binding specificity of Nck1 and Nck2 Src homology 2 domains., Frese S, Schubert WD, Findeis AC, Marquardt T, Roske YS, Stradal TE, Heinz DW, J Biol Chem. 2006 Jun 30;281(26):18236-45. Epub 2006 Apr 24. PMID:16636066
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