Structure of the angiopoietin-2 receptor binding domain and identification of surfaces involved in Tie2 recognition.
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Barton WA, Tzvetkova D, Nikolov DB
Structure of the angiopoietin-2 receptor binding domain and identification of surfaces involved in Tie2 recognition.
Structure. 2005 May;13(5):825-32. doi: 10.1016/j.str.2005.03.009.
- PubMed ID
- 15893672 [ View in PubMed]
- Abstract
The angiopoietins comprise a small class of secreted glycoproteins that play crucial roles in the maturation and maintenance of the mammalian vascular and lymphatic systems. They exert their effects through a member of the tyrosine kinase receptor family, Tie2. Angiopoietin/Tie2 signaling is unique among tyrosine kinase receptor-ligand systems in that distinct angiopoietin ligands, although highly homologous, can function as agonists or antagonists in a context-dependent manner. In an effort to understand this molecular dichotomy, we have crystallized and determined the 2.4 A crystal structure of the Angiopoietin-2 (Ang2) receptor binding region. The structure reveals a fibrinogen fold with a unique C-terminal P domain. Conservation analysis and structure-based mutagenesis identify a groove on the Ang2 molecular surface that mediates receptor recognition.