1ckb

STRUCTURAL BASIS FOR THE SPECIFIC INTERACTION OF LYSINE-CONTAINING PROLINE-RICH PEPTIDES WITH THE N-TERMINAL SH3 DOMAIN OF C-CRK

spinqualitylabelsall models 1ckb, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1ckb is a 2 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: PCR PRODUCT (LK3 transgenic mice) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [CRK_MOUSE] The Crk-I and Crk-II forms differ in their biological activities. Crk-II has less transforming activity than Crk-I. Crk-II mediates attachment-induced MAPK8 activation, membrane ruffling and cell motility in a Rac-dependent manner. Involved in phagocytosis of apoptotic cells and cell motility via its interaction with DOCK1 and DOCK4. May regulate the EFNA5-EPHA3 signaling. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Adapter molecule crk

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