Structure of the angiopoietin-2 receptor binding domain and identification of surfaces involved in Tie2 recognition.
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.
Barton
William A
WA
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.
Tzvetkova
Dorothea
D
Nikolov
Dimitar B
DB
D000595:Amino Acid Sequence; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D003461:Crystallography; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D017434:Protein Structure, Tertiary; D042787:Receptor, TIE-2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D042787:Receptor, TIE-2; D002118:Calcium