2c5d
From Proteopedia
Revision as of 23:16, 30 March 2008
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| , resolution 3.3Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , , | ||||||
| Activity: | Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE OF A MINIMAL GAS6-AXL COMPLEX
Overview
Receptor tyrosine kinases of the Axl family are activated by the vitamin K-dependent protein Gas6. Axl signalling plays important roles in cancer, spermatogenesis, immunity, and platelet function. The crystal structure at 3.3 A resolution of a minimal human Gas6/Axl complex reveals an assembly of 2:2 stoichiometry, in which the two immunoglobulin-like domains of the Axl ectodomain are crosslinked by the first laminin G-like domain of Gas6, with no direct Axl/Axl or Gas6/Gas6 contacts. There are two distinct Gas6/Axl contacts of very different size, both featuring interactions between edge beta-strands. Structure-based mutagenesis, protein binding assays and receptor activation experiments demonstrate that both the major and minor Gas6 binding sites are required for productive transmembrane signalling. Gas6-mediated Axl dimerisation is likely to occur in two steps, with a high-affinity 1:1 Gas6/Axl complex forming first. Only the minor Gas6 binding site is highly conserved in the other Axl family receptors, Sky/Tyro3 and Mer. Specificity at the major contact is suggested to result from the segregation of charged and apolar residues to opposite faces of the newly formed beta-sheet.
About this Structure
2C5D is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for Gas6-Axl signalling., Sasaki T, Knyazev PG, Clout NJ, Cheburkin Y, Gohring W, Ullrich A, Timpl R, Hohenester E, EMBO J. 2006 Jan 11;25(1):80-7. Epub 2005 Dec 15. PMID:16362042
Page seeded by OCA on Mon Mar 31 02:16:35 2008
Categories: Homo sapiens | Protein complex | Transferase | Cheburkin, Y. | Clout, N J. | Goehring, W. | Hohenester, E. | Knyazev, P G. | Sasaki, T. | Timpl, R. | Ullrich, A. | Egf-like domain | Growth regulation | Immunoglobulin-like domain | Laminin g-like domain | Receptor | Receptor tyrosine kinase | Vitamin k-dependent protein
