PDBsum entry 2gy7

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protein ligands metals Protein-protein interface(s) links
Signaling protein PDB id
Protein chains
216 a.a. *
423 a.a. *
SO4 ×2
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: Angiopoietin-2/tie2 complex crystal structure
Structure: Angiopoietin-2. Chain: a. Fragment: angiopoietin-2 receptor binding domain (residues synonym: ang-2. Engineered: yes. Angiopoietin-1 receptor. Chain: b. Fragment: tie2 ligand-binding domain (residues 23-445). Synonym: tyrosine-protein kinase receptor tie-2, htie2, tyr
Source: Homo sapiens. Human. Organism_taxid: 9606. Expression_system_cell_line: hek 293. Gene: tek, tie2.
3.70Å     R-factor:   0.240     R-free:   0.317
Authors: W.A.Barton,D.B.Nikolov
Key ref:
W.A.Barton et al. (2006). Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex. Nat Struct Mol Biol, 13, 524-532. PubMed id: 16732286 DOI: 10.1038/nsmb1101
09-May-06     Release date:   06-Jun-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
O15123  (ANGP2_HUMAN) -  Angiopoietin-2
496 a.a.
216 a.a.*
Protein chain
Pfam   ArchSchema ?
Q02763  (TIE2_HUMAN) -  Angiopoietin-1 receptor
1124 a.a.
423 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chain B: E.C.  - Receptor protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Bound ligand (Het Group name = NAG)
matches with 47.62% similarity
+ [protein]-L-tyrosine phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     integral to plasma membrane   1 term 
  Biological process     transmembrane receptor protein tyrosine kinase signaling pathway   2 terms 
  Biochemical function     receptor tyrosine kinase binding     3 terms  


DOI no: 10.1038/nsmb1101 Nat Struct Mol Biol 13:524-532 (2006)
PubMed id: 16732286  
Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex.
W.A.Barton, D.Tzvetkova-Robev, E.P.Miranda, M.V.Kolev, K.R.Rajashankar, J.P.Himanen, D.B.Nikolov.
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.
  Selected figure(s)  
Figure 1.
Figure 1. Structure of the Tie2 ligand-binding region. (a) Schematic representation of the domain organization of the Tie receptors. Red, Ig1; blue, Ig2; green, Ig3; yellow, EGF1; purple, EGF2; orange, EGF3; gray, the three fibronectin type III (FNIII) repeats and the cytoplasmic tyrosine kinase catalytic domain. (b) The ligand-binding extracellular region of Tie2, colored as in a. Asparagine-linked carbohydrate groups are shown in ball-and-stick format. (c) The EGF region of Tie2, colored as in a. The 12 disulfide bonds (four in each EGF repeat) are shown in gray ball-and-stick format. (d) The Tie2 ligand-binding region. Red, the large and highly curved trans-domain 11-stranded -sheet comprised of strands Ig1(D-E-B-A-)-EGF2(C-D)-Ig2(A'-G-F-C-C').
Figure 4.
Figure 4. Crystal structure of the Ang2–Tie2 complex. Shown are two views of the complex related by a 90° rotation around the y-axis. Yellow, P domain of Ang2; red, the rest of Ang2; green, Tie2 Ig2; blue, the rest of Tie2; black sphere, bound Ca^2+. Asparagine-linked carbohydrate groups are shown in ball-and-stick format.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2006, 13, 524-532) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20651738 H.Huang, A.Bhat, G.Woodnutt, and R.Lappe (2010).
Targeting the ANGPT-TIE2 pathway in malignancy.
  Nat Rev Cancer, 10, 575-585.  
20227369 T.C.Seegar, B.Eller, D.Tzvetkova-Robev, M.V.Kolev, S.C.Henderson, D.B.Nikolov, and W.A.Barton (2010).
Tie1-Tie2 interactions mediate functional differences between angiopoietin ligands.
  Mol Cell, 37, 643-655.  
19922791 T.M.Hansen, H.Singh, T.A.Tahir, and N.P.Brindle (2010).
Effects of angiopoietins-1 and -2 on the receptor tyrosine kinase Tie2 are differentially regulated at the endothelial cell surface.
  Cell Signal, 22, 527-532.  
19234476 H.G.Augustin, G.Young Koh, G.Thurston, and K.Alitalo (2009).
Control of vascular morphogenesis and homeostasis through the angiopoietin-Tie system.
  Nat Rev Mol Cell Biol, 10, 165-177.  
18458089 R.Mor-Cohen, N.Rosenberg, M.Landau, J.Lahav, and U.Seligsohn (2008).
Specific cysteines in beta3 are involved in disulfide bond exchange-dependent and -independent activation of alphaIIbbeta3.
  J Biol Chem, 283, 19235-19244.  
18266978 T.Makinde, and D.K.Agrawal (2008).
Intra and extravascular transmembrane signalling of angiopoietin-1-Tie2 receptor in health and disease.
  J Cell Mol Med, 12, 810-828.  
17341311 V.P.Nguyen, S.H.Chen, J.Trinh, H.Kim, B.L.Coomber, and D.J.Dumont (2007).
Differential response of lymphatic, venous and arterial endothelial cells to angiopoietin-1 and angiopoietin-2.
  BMC Cell Biol, 8, 10.  
16849318 P.R.Macdonald, P.Progias, B.Ciani, S.Patel, U.Mayer, M.O.Steinmetz, and R.A.Kammerer (2006).
Structure of the extracellular domain of Tie receptor tyrosine kinases and localization of the angiopoietin-binding epitope.
  J Biol Chem, 281, 28408-28414.  
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