Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex Journal Article

Authors: Barton, W. A.; Tzvetkova Robev, D.; Miranda, E. P.; Kolev, M. V.; Rajashankar, K. R.; Himanen, J. P.; Nikolov, D. B.
Article Title: Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex
Abstract: The Tie receptor tyrosine kinases and their angiopoietin (Ang) ligands play central roles in developmental and tumor-induced angiogenesis. Here we present the crystal structures of the Tie2 ligand-binding region alone and in complex with Ang2. 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. 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. Ang2-Tie2 recognition is similar to antibody-protein antigen recognition, including the location of the ligand-binding site within the Ig fold. 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. © 2006 Nature Publishing Group.
Keywords: epidermal growth factor; protein conformation; protein domain; protein binding; calcium; protein interaction; prediction; amino acid sequence; molecular sequence data; sequence homology, amino acid; immunoglobulin g; molecular recognition; antigen recognition; binding site; crystal structure; models, molecular; crystallography, x-ray; conformational transition; protein structure; angiopoietin receptor; receptor, tie-2; ligand binding; mutagenesis; fibrinogen; chromatography, gel; angiopoietin; angiopoietin-2; alismataceae
Journal Title: Nature Structural and Molecular Biology
Volume: 13
Issue: 6
ISSN: 1545-9993
Publisher: Nature Publishing Group  
Date Published: 2006-06-01
Start Page: 524
End Page: 532
Language: English
DOI: 10.1038/nsmb1101
PUBMED: 16732286
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 28" - "Export Date: 4 June 2012" - "CODEN: NSMBC" - "Source: Scopus"
Citation Impact
MSK Authors
  1. William A Barton
    17 Barton
  2. Dimitar B Nikolov
    73 Nikolov
  3. Juha P Himanen
    43 Himanen
  4. Momchil V Kolev
    7 Kolev
  5. Dorothea Dimitrova Robev
    12 Robev