2C5D
Structure of a minimal Gas6-Axl complex
Summary for 2C5D
| Entry DOI | 10.2210/pdb2c5d/pdb |
| Related | 1H30 |
| Descriptor | GROWTH-ARREST-SPECIFIC PROTEIN 6 PRECURSOR, TYROSINE-PROTEIN KINASE RECEPTOR UFO, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | signaling protein/receptor, growth regulation-complex, vitamin k-dependent protein, laminin g-like domain, receptor tyrosine kinase, immunoglobulin-like domain, growth regulation, egf-like domain, receptor, signaling protein-receptor complex |
| Biological source | HOMO SAPIENS (HUMAN) More |
| Total number of polymer chains | 4 |
| Total formula weight | 136619.93 |
| Authors | Sasaki, T.,Knyazev, P.G.,Clout, N.J.,Cheburkin, Y.,Goehring, W.,Ullrich, A.,Timpl, R.,Hohenester, E. (deposition date: 2005-10-26, release date: 2005-12-19, Last modification date: 2024-11-20) |
| Primary citation | Sasaki, T.,Knyazev, P.G.,Clout, N.J.,Cheburkin, Y.,Goehring, W.,Ullrich, A.,Timpl, R.,Hohenester, E. Structural Basis for Gas6-Axl Signalling. Embo J., 25:80-, 2006 Cited by PubMed Abstract: 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. PubMed: 16362042DOI: 10.1038/SJ.EMBOJ.7600912 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.3 Å) |
Structure validation
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