Science, Vol.281, No.5381, 1357-1360, 1998
Structure and Asn-Pro-Phe binding pocket of the Eps15 homology domain
Eps15 homology (EH) domains are eukaryotic signaling modules that recognize proteins containing Asn-Pro-Phe (NPF) sequences. The structure of the central EH domain of Eps15 has been solved by heteronuclear magnetic resonance spectroscopy. The fold consists of a pair of EF hand motifs, the second of Which binds tightly to calcium. The NPF peptide is bound in a hydrophobic pocket between two a helices, and binding is mediated by a critical aromatic interaction as revealed by structure-based mutagenesis. The fold is predicted to be highly conserved among 30 identified EH domains and provides a structural basis for defining EH-mediated events in protein trafficking and growth factor signaling.
Keywords:TYROSINE KINASE SUBSTRATE;ANGSTROM RESOLUTION;TERMINAL DOMAIN;EH DOMAIN;PROTEIN;NMR;ASSOCIATION