A repertoire library that allows the selection of synthetic SH2ITALT with altered binding specificities

Maria Grazia Malabarba, Elisabetta Milia, Mario Faretta, Raffaella Zamponi, Pier Giuseppe Pelicci, Pier Paolo Di Fiore

Research output: Contribution to journalArticlepeer-review

Abstract

Tyrosine phosphorylation is one of the major mechanisms involved in the intracellular propagation of external signals. Strategies aimed at interfering with this process might allow the control of several cellular phenotypes. SH2 domains mediate protein-protein interactions by recognizing phosphotyrosine (pY) residues in the context of specific phosphopeptides. We created an SH2-scaffolded repertoire library by randomly mutagenizing five critical amino acid positions in the specificity-determining region of the PLCγ C-terminal SH2 domain. Synthetic SH2 domains were selected from the library using biotinylated phosphopeptides derived from a natural PLCγ-SH2 ligand as well as unrelated SH2 ligands. The isolated SH2s displayed high binding affinity constants for the selecting peptides and were capable of interacting with the corresponding proteins.

Original languageEnglish
Pages (from-to)5186-5194
Number of pages9
JournalOncogene
Volume20
Issue number37
DOIs
Publication statusPublished - Aug 23 2001

Keywords

  • Phosphotyrosine
  • Scaffold
  • Scaffold library
  • SH2

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Fingerprint Dive into the research topics of 'A repertoire library that allows the selection of synthetic SH2ITALT with altered binding specificities'. Together they form a unique fingerprint.

Cite this