2C5D

Structure of a minimal Gas6-Axl complex

2C5D の概要

• エントリーDOI: 10.2210/pdb2c5d/pdb
• 関連するPDBエントリー: 1H30
• 分子名称: 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)
• 機能のキーワード: 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
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 136619.93

構造登録者

Sasaki, T.,Knyazev, P.G.,Clout, N.J.,Cheburkin, Y.,Goehring, W.,Ullrich, A.,Timpl, R.,Hohenester, E. (登録日: 2005-10-26, 公開日: 2005-12-19, 最終更新日: 2024-11-20)

主引用文献

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

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: 16362042
DOI: 10.1038/SJ.EMBOJ.7600912

実験手法

X-RAY DIFFRACTION (3.3 Å)