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

ABSTRACT: 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.

SUBMITTER: Feng S

PROVIDER: S-EPMC40367 | biostudies-other | 1995 Dec

REPOSITORIES: biostudies-other

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

Feng S S Kasahara C C Rickles R J RJ Schreiber S L SL

Proceedings of the National Academy of Sciences of the United States of America 19951201 26

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 occupi ...[more]

PMID: 8618911

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