PMID: 16732286

 

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Title : Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2- Tie2 complex

Abstract :

1. The Tie receptor tyrosine kinases and their angiopoietin ( Ang ) ligands play central roles in developmental and tumor-induced angiogenesis
2. Here we present the crystal structures of the Tie2 ligand-binding region alone and in complex with Ang2
3. In contrast to prediction, Tie2 contains not two but three immunoglobulin (Ig) domains , which fold together with the three epidermal growth factor domains into a compact, arrowhead-shaped structure
4. Ang2 binds at the tip of the arrowhead utilizing a lock-and-key mode of ligand recognition-unique for a receptor kinase-where two complementary surfaces interact with each other with no domain rearrangements and little conformational change in either molecule
5. Ang2- Tie2 recognition is similar to antibody-protein antigen recognition, including the location of the ligand-binding site within the Ig fold
6. Analysis of the structures and structure-based mutagenesis provide insight into the mechanism of receptor activation and support the hypothesis that all angiopoietins interact with Tie2 in a structurally similar manner.