2CI9

Nck1 SH2-domain in complex with a dodecaphosphopeptide from EPEC protein Tir

Summary for 2CI9

• Entry DOI: 10.2210/pdb2ci9/pdb
• Related: 2CI8 2CIA 2CUB
• Descriptor: CYTOPLASMIC PROTEIN NCK1, TRANSLOCATED INTIMIN RECEPTOR (3 entities in total)
• Functional Keywords: protein-binding, sh2-domain-complex, protein binding
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 4
• Total formula weight: 26439.42

Authors

Frese, S.,Schubert, W.-D.,Findeis, A.C.,Marquardt, T.,Roske, Y.S.,Stradal, T.E.B.,Heinz, D.W. (deposition date: 2006-03-17, release date: 2006-04-24, Last modification date: 2024-05-01)

Primary citation

Frese, S.,Schubert, W.-D.,Findeis, A.C.,Marquardt, T.,Roske, Y.S.,Stradal, T.E.B.,Heinz, D.W.
The Phosphotyrosine Peptide Binding Specificity of Nck1 and Nck2 Src Homology 2 Domains.
J.Biol.Chem., 281:18236-, 2006

PubMed Abstract: 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.

PubMed: 16636066
DOI: 10.1074/JBC.M512917200

Experimental method

X-RAY DIFFRACTION (1.5 Å)