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| STRUCTURAL DETERMINANTS OF PEPTIDE-BINDING ORIENTATION AND OF SEQUENCE SPECIFICITY IN SH3 DOMAINS |
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| Author(s): LIM WA, RICHARDS FM, FOX RO |
| Source: NATURE Volume: 372 Issue: 6504 Pages: 375-379 Published: NOV 24 1994 |
| Times Cited: 359 References: 28 |
| Abstract: THE Src-homology-3 (SH3) domains of the Caenorhabditis elegans protein SEM-5 and its human and Drosophila homologues, Grb2 and Drk (refs 1-4), bind proline-rich sequences found in the nucleotide-exchange factor Sos as part of their proposed function linking receptor tyrosine kinase activation to Ras activation(5-7). Here we report the crystal structure at 2.0 Angstrom resolution of the carboxy-terminal SH3 domain from SEM-5 complexed to the mSos-derived amino-acid sequence PPPVPPRRR. The peptide is found to bind in an orientation ('minus') that is precisely opposite to that observed previously ('plus' orientation) in other SH3-peptide complexes(8,9). This novel ability of peptide-recognition proteins to recognize peptides in two distinct modes may play an important role in the signalling specificity of pathways involving SH3 domains. Comparison of this structure with other SH3 complexes reveals how a conserved binding face can be used to recognize peptides in different orientations, and why the Sos peptide binds in this particular orientation. |
| Document Type: Article |
| Language: English |
| Reprint Address: LIM, WA (reprint author), YALE UNIV, DEPT MOLEC BIOPHYS & BIOCHEM, POB 6666, NEW HAVEN, CT 06520 USA |
Addresses:
1. YALE UNIV, HOWARD HUGHES MED INST, NEW HAVEN, CT 06520 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: PU287 |
| ISSN: 0028-0836 |
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