SH3 domains constitute a family of protein-protein interaction modules that bind to peptides displaying an X-proline-X-X-proline (XPXXP) consensus. We report that the SH3 domain of Eps8, a substrate of receptor and non-receptor tyrosine kinases, displays a novel and unique binding preference. By a combination of approaches including (i) screening of phage-displayed random peptide libraries, (ii) mapping of the binding regions on three physiological interactors of Eps8, (iii) alanine scanning of binding peptides and (iv) in vitro cross-linking, we demonstrate that a proline-X-X-aspartate-tyrosine (PXXDY) consensus is indispensable for binding to the SH3 domain of Eps8. Screening of the Expressed Sequence Tags database allowed the identification of three Eps8-related genes, whose SH3s also display unusual binding preferences and constitute a phylogenetically distinct subfamily within the SH3 family. Thus, Eps8 identifies a novel family of SH3-containing proteins that do not bind to canonical XPXXP-containing peptides, and that establish distinct interactions in the signaling network.
A novel peptide-SH3 interaction / A. M. Mongioví, P. R. Romano, S. Panni, M. Mendoza, W. T. Wong, A. Musacchio, G. Cesareni, P. P. Di Fiore. - In: EMBO JOURNAL. - ISSN 0261-4189. - 18:19(1999 Oct 01), pp. 5300-9-5309.
|Titolo:||A novel peptide-SH3 interaction|
DI FIORE, PIER PAOLO (Ultimo)
|Parole Chiave:||Animals; Intracellular Signaling Peptides and Proteins; Humans; Recombinant Fusion Proteins; Amino Acid Sequence; Mice; Protein Binding; src Homology Domains; Peptide Fragments; Amino Acid Motifs; Adaptor Proteins, Signal Transducing; Molecular Sequence Data; Proteins; Cytoskeletal Proteins; Consensus Sequence; Sequence Homology, Amino Acid|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||1-ott-1999|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/emboj/18.19.5300|
|Appare nelle tipologie:||01 - Articolo su periodico|