| First Author | Ferguson MR | Year | 2004 |
| Journal | Protein Sci | Volume | 13 |
| Issue | 3 | Pages | 626-32 |
| PubMed ID | 14978303 | Mgi Jnum | J:200318 |
| Mgi Id | MGI:5508277 | Doi | 10.1110/ps.03470504 |
| Citation | Ferguson MR, et al. (2004) Directed discovery of bivalent peptide ligands to an SH3 domain. Protein Sci 13(3):626-32 |
| abstractText | The Caenorhabditis elegans SEM-5 SH3 domains recognize proline-rich peptide segments with modest affinity. We developed a bivalent peptide ligand that contains a naturally occurring proline-rich binding sequence, tethered by a glycine linker to a disulfide-closed loop segment containing six variable residues. The glycine linker allows the loop segment to explore regions of greatest diversity in sequence and structure of the SH3 domain: the RT and n-Src loops. The bivalent ligand was optimized using phage display, leading to a peptide (PP-G(4)-L) with 1000-fold increased affinity for the SEM-5 C-terminal SH3 domain over that of a natural ligand. NMR analysis of the complex confirms that the peptide loop segment is targeted to the RT and n-Src loops and parts of the beta-sheet scaffold of this SH3 domain. This binding region is comparable to that targeted by a natural non-PXXP peptide to the p67(phox) SH3 domain, a region not known to be targeted in the Grb2 SH3 domain family. PP-G(4)-L may aid in the discovery of additional binding partners of Grb2 family SH3 domains. |
