2cia
From Proteopedia
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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. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[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: ACE]] | [[Category: ACE]] | ||
[[Category: IPA]] | [[Category: IPA]] | ||
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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 16:49:03 2008'' |
Revision as of 14:49, 21 February 2008
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HUMAN NCK2 SH2-DOMAIN IN COMPLEX WITH A DECAPHOSPHOPEPTIDE FROM TRANSLOCATED INTIMIN RECEPTOR (TIR) OF EPEC
Overview
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.
About this Structure
2CIA is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 16:49:03 2008
Categories: Homo sapiens | Protein complex | Findeis, A C. | Frese, S. | Heinz, D W. | Marquardt, T. | Roske, Y S. | Schubert, W D. | Stradal, T E.B. | ACE | IPA | MPD | Binding specificity | Phosphorylation | Sh2-domain | Sh3 domain
