2c5d
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Receptor tyrosine kinases of the Axl family are activated by the vitamin | + | 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== | ==About this Structure== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Transferred entry: 2 | + | [[Category: Transferred entry: 2 7.10 1 and 2 7.10 2]] |
[[Category: Cheburkin, Y.]] | [[Category: Cheburkin, Y.]] | ||
| - | [[Category: Clout, N | + | [[Category: Clout, N J.]] |
[[Category: Goehring, W.]] | [[Category: Goehring, W.]] | ||
[[Category: Hohenester, E.]] | [[Category: Hohenester, E.]] | ||
| - | [[Category: Knyazev, P | + | [[Category: Knyazev, P G.]] |
[[Category: Sasaki, T.]] | [[Category: Sasaki, T.]] | ||
[[Category: Timpl, R.]] | [[Category: Timpl, R.]] | ||
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[[Category: vitamin k-dependent protein]] | [[Category: vitamin k-dependent protein]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:45:05 2008'' |
Revision as of 14:45, 21 February 2008
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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 with , and as ligands. Active as Transferred entry: 2.7.10.1 and 2.7.10.2, with EC number 2.7.1.112 Known structural/functional Site: . 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 Thu Feb 21 16:45:05 2008
Categories: Homo sapiens | Protein complex | Transferred entry: 2 7.10 1 and 2 7.10 2 | Cheburkin, Y. | Clout, N J. | Goehring, W. | Hohenester, E. | Knyazev, P G. | Sasaki, T. | Timpl, R. | Ullrich, A. | CA | NI | SO4 | Egf-like domain | Growth regulation | Immunoglobulin-like domain | Laminin g-like domain | Receptor | Receptor tyrosine kinase | Vitamin k-dependent protein
