Poster abstracts

Poster number 15 submitted by Yanyan Zhang

The noncanonical binding stoichiometry of 2:1 for SHP2 NSH2 with classIV binding ligands-validation and significance

Yanyan Zhang (Chemistry), Jinjin Zhang, Chunhua Yuan, Charles Bell, Dehua Pei

Abstract:
Protein tyrosine phosphatase SHP2 participates in signaling events through the interaction of its tandem SH2 domains with various activated receptors. The binding specificity of its N-terminal SH2 (N-SH2) domain was previously determined by a combinatorial library approach. It was found that the N-SH2 domain could recognize four distinct classes of binding motifs. In this study, the co-crystal structure of a class IV motif, VIpYFVP, bound to the N-SH2 domain was determined, which revealed a noncanonical 2:1 (peptide: protein) binding mode. This binding mode was confirmed in solution phase by ¹⁵N-¹H HSQC, ¹³C-¹H HSQC, and ³¹P NMR experiments.

Keywords: SHP2 SH2, Soichiometry, X-ray, NMR