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2c5d
From Proteopedia
STRUCTURE OF A MINIMAL GAS6-AXL COMPLEX
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2c5d is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Sasaki T, Knyazev PG, Clout NJ, Cheburkin Y, Gohring W, Ullrich A, Timpl R, Hohenester E. Structural basis for Gas6-Axl signalling. EMBO J. 2006 Jan 11;25(1):80-7. Epub 2005 Dec 15. PMID:16362042
- Sasaki T, Knyazev PG, Cheburkin Y, Gohring W, Tisi D, Ullrich A, Timpl R, Hohenester E. Crystal structure of a C-terminal fragment of growth arrest-specific protein Gas6. Receptor tyrosine kinase activation by laminin G-like domains. J Biol Chem. 2002 Nov 15;277(46):44164-70. Epub 2002 Sep 5. PMID:12218057 doi:10.1074/jbc.M207340200
- Heiring C, Dahlback B, Muller YA. Ligand recognition and homophilic interactions in Tyro3: structural insights into the Axl/Tyro3 receptor tyrosine kinase family. J Biol Chem. 2004 Feb 20;279(8):6952-8. Epub 2003 Nov 17. PMID:14623883 doi:10.1074/jbc.M311750200
Categories: Homo sapiens | Transferase | Cheburkin, Y. | Clout, N J. | Goehring, W. | Hohenester, E. | Knyazev, P G. | Sasaki, T. | Timpl, R. | Ullrich, A. | Egf-like domain | Growth regulation | Growth regulation/complex | Immunoglobulin-like domain | Laminin g-like domain | Receptor | Receptor tyrosine kinase | Signaling protein/receptor | Vitamin k-dependent protein
