2c5d

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Template:STRUCTURE 2c5d

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 Sat May 3 21:16:38 2008