1ckb
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(New page: 200px<br /><applet load="1ckb" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ckb, resolution 1.90Å" /> '''STRUCTURAL BASIS FOR...)
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Revision as of 10:24, 20 November 2007
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STRUCTURAL BASIS FOR THE SPECIFIC INTERACTION OF LYSINE-CONTAINING PROLINE-RICH PEPTIDES WITH THE N-TERMINAL SH3 DOMAIN OF C-CRK
Overview
BACKGROUND: Proline-rich segments in the guanine nucleotide exchange, factor C3G bind much more strongly to the N-terminal Src homology 3 domain, (SH3-N) of the proto-oncogene product c-Crk than to other SH3 domains. The, presence of a lysine instead of an arginine in the peptides derived from, C3G appears to be crucial for this specificity towards c-Crk. RESULTS: In, order to understand the chemical basis of this specificity we have, determined the crystal structure of Crk SH3-N in complex with a high, affinity peptide from C3G (PPPALPPKKR, Kd approximately 2 microM) at 1.5 A, resolution. The peptide adopts a polyproline type II helix that binds, as, dictated by electrostatic complementarity, in reversed orientation, relative to the orientation seen in the earliest structures of SH3-peptide, complexes. A lysine in the C3G peptide is tightly coordinated by three, acidic residues in the SH3 domain. In contrast, the co-crystal structure, of c-Crk SH3-N and a peptide containing an arginine at the equivalent, position (determined at 1.9 A resolution) reveals non-optimal geometry for, the arginine and increased disorder. CONCLUSIONS: The c-Crk SH3 domain, engages in an unusual lysine-specific interaction that is rarely seen in, protein structures, and which appears to be a key determinant of its, unique ability to bind the C3G peptides with high affinity.
About this Structure
1CKB is a Single protein structure of sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA.
Reference
Structural basis for the specific interaction of lysine-containing proline-rich peptides with the N-terminal SH3 domain of c-Crk., Wu X, Knudsen B, Feller SM, Zheng J, Sali A, Cowburn D, Hanafusa H, Kuriyan J, Structure. 1995 Feb 15;3(2):215-26. PMID:7735837
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