Specific interactions outside the proline-rich core of two classes of Src homology 3 ligands.

作者：S Feng, Chiyoshi Kasahara, Richard J. Rickles, Stuart L. Schreiber · 发表于：Proceedings of the National Academy of Sciences · 年份：1995 · DOI：10.1073/pnas.92.26.12408 · 被引用次数：247 · 研究领域：Monoclonal and Polyclonal Antibodies Research、Chemical Synthesis and Analysis、Glycosylation and Glycoproteins Research

Two dodecapeptides belonging to distinct classes of Src homology 3 (SH3) ligands and selected from biased phage display libraries were used to investigate interactions between a specificity pocket in the Src SH3 domain and ligant residues flanking the proline-rich core. The solution structures of c-Src SH3 complexed with these peptides were solved by NMR. In addition to proline-rich, polyproline type II helix-forming core, the class I and II ligands each possesses a flanking sequence that occupies a large pocket between the RT and n-Src loops of the SH3 domain. Structural and mutational analyses illustrate how the two classes of SH3 ligands exploit a specificity pocket on the receptor differently to increase binding affinity and specificity.