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Science 28 August 1998:
Vol. 281. no. 5381, pp. 1357 - 1360
DOI: 10.1126/science.281.5381.1357
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Reports

Structure and Asn-Pro-Phe Binding Pocket of the Eps15 Homology Domain

Tonny de Beer, Royston E. Carter, Katherine E. Lobel-Rice, Alexander Sorkin, Michael Overduin *

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 alpha  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.

Department of Pharmacology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.
*   To whom correspondence should be addressed. E-mail: MichaelOverduin{at}UCHSC.edu

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