2KXC: 1H, 13C, and 15N Chemical Shift Assignments for IRTKS-SH3 and EspFu-R47 complex

Src homology 3 (SH3) domains are globular protein interaction modules that regulate cell behavior. The classic SH3 ligand-binding site accommodates a hydrophobic PxxP motif and a positively charged specificity-determining residue. We have determined the NMR structure of insulin receptor tyrosine kinase substrate (IRTKS) SH3 domain in complex with a repeat from Escherichia coli-secreted protein F-like protein encoded on prophage U (EspF(U)), a translocated effector of enterohemorrhagic E. coli that commandeers the mammalian actin assembly machinery. EspF(U)-IRTKS interaction is among the highest affinity natural SH3 ligands. Our complex structure reveals a unique type of SH3 interaction based on recognition of tandem PxxP motifs in the ligand. Strikingly, the specificity pocket of IRTKS SH3 has evolved to accommodate a polyproline type II helical peptide analogously to docking of the canonical PxxP by the conserved IRTKS SH3 proline-binding pockets. This cooperative binding explains the high-affinity SH3 interaction and is required for EspF(U)-IRTKS interaction in mammalian cells as well as the formation of localized actin "pedestals" beneath bound bacteria. Importantly, tandem PxxP motifs are also found in mammalian ligands and have been shown to contribute to IRTKS SH3 recognition similarly.
PDB ID: 2KXCDownload
MMDB ID: 86171
PDB Deposition Date: 2010/4/30
Updated in MMDB: 2010/11
Experimental Method:
solution nmr
Source Organism:
Escherichia coli O157:H7
Similar Structures:
Biological Unit for 2KXC: dimeric; determined by author
Molecular Components in 2KXC
Label Count Molecule
Proteins (2 molecules)
Brain-specific Angiogenesis Inhibitor 1-associated Protein 2-like Protein 1(Gene symbol: BAIAP2L1)
Molecule annotation
Espf-like Protein
Molecule annotation
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Citing MMDB