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

Author:

de Beer Tonny1,Carter Royston E.1,Lobel-Rice Katherine E.1,Sorkin Alexander1,Overduin Michael1

Affiliation:

1. Department of Pharmacology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.

Abstract

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 α 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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