A novel peptide-SH3 interaction

Adriana Maria Mongioví, Pascale R. Romano, Simona Panni, Manuel Mendoza, William T. Wong, Andrea Musacchio, Gianni Cesarenib, Pier Paolo Di Fiore

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5300-5309
Number of pages10
JournalEMBO Journal
Volume18
Issue number19
DOIs
Publication statusPublished - Oct 1 1999

Fingerprint

Proline
src Homology Domains
Peptides
Screening
Peptide Library
Proteins
Bacteriophages
Expressed Sequence Tags
Aspartic Acid
Alanine
Protein-Tyrosine Kinases
Tyrosine
Genes
Databases
Scanning
Substrates

Keywords

  • Eps8
  • SH3
  • Signal transduction

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Mongioví, A. M., Romano, P. R., Panni, S., Mendoza, M., Wong, W. T., Musacchio, A., ... Di Fiore, P. P. (1999). A novel peptide-SH3 interaction. EMBO Journal, 18(19), 5300-5309. https://doi.org/10.1093/emboj/18.19.5300

A novel peptide-SH3 interaction. / Mongioví, Adriana Maria; Romano, Pascale R.; Panni, Simona; Mendoza, Manuel; Wong, William T.; Musacchio, Andrea; Cesarenib, Gianni; Di Fiore, Pier Paolo.

In: EMBO Journal, Vol. 18, No. 19, 01.10.1999, p. 5300-5309.

Research output: Contribution to journalArticle

Mongioví, AM, Romano, PR, Panni, S, Mendoza, M, Wong, WT, Musacchio, A, Cesarenib, G & Di Fiore, PP 1999, 'A novel peptide-SH3 interaction', EMBO Journal, vol. 18, no. 19, pp. 5300-5309. https://doi.org/10.1093/emboj/18.19.5300
Mongioví AM, Romano PR, Panni S, Mendoza M, Wong WT, Musacchio A et al. A novel peptide-SH3 interaction. EMBO Journal. 1999 Oct 1;18(19):5300-5309. https://doi.org/10.1093/emboj/18.19.5300
Mongioví, Adriana Maria ; Romano, Pascale R. ; Panni, Simona ; Mendoza, Manuel ; Wong, William T. ; Musacchio, Andrea ; Cesarenib, Gianni ; Di Fiore, Pier Paolo. / A novel peptide-SH3 interaction. In: EMBO Journal. 1999 ; Vol. 18, No. 19. pp. 5300-5309.
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