PDBsum entry 1z3u

Go to PDB code: 
protein metals links
Signaling protein PDB id
Protein chain
216 a.a. *
_CA ×4
Waters ×379
* Residue conservation analysis
PDB id:
Name: Signaling protein
Title: Structure of the angiopoietin-2 recptor binding domain and identification of surfaces involved in tie2 recognition
Structure: Angiopoietin-2. Chain: a, b, c, d. Fragment: receptor binding domain (residues 281-496). Synonym: ang-2. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
2.25Å     R-factor:   0.246     R-free:   0.278
Authors: W.A.Barton,D.Tzvetkova,D.B.Nikolov
Key ref:
W.A.Barton et al. (2005). Structure of the angiopoietin-2 receptor binding domain and identification of surfaces involved in Tie2 recognition. Structure, 13, 825-832. PubMed id: 15893672 DOI: 10.1016/j.str.2005.03.009
14-Mar-05     Release date:   12-Jul-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
O15123  (ANGP2_HUMAN) -  Angiopoietin-2
496 a.a.
216 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     receptor tyrosine kinase binding     1 term  


DOI no: 10.1016/j.str.2005.03.009 Structure 13:825-832 (2005)
PubMed id: 15893672  
Structure of the angiopoietin-2 receptor binding domain and identification of surfaces involved in Tie2 recognition.
W.A.Barton, D.Tzvetkova, D.B.Nikolov.
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.
  Selected figure(s)  
Figure 5.
Figure 5. Structure of the F468A/Y474A/Y475A Ang2-RBD Mutant
The structure is (blue) superimposed on the structure of the wild-type protein (red). Mutated residues are shown in yellow ball-and-stick format.
  The above figure is reprinted by permission from Cell Press: Structure (2005, 13, 825-832) copyright 2005.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21439481 N.Singla, H.Erdjument-Bromage, J.P.Himanen, T.W.Muir, and D.B.Nikolov (2011).
A semisynthetic Eph receptor tyrosine kinase provides insight into ligand-induced kinase activation.
  Chem Biol, 18, 361-371.  
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.  
19892701 T.Thomsen, J.B.Moeller, A.Schlosser, G.L.Sorensen, S.K.Moestrup, N.Palaniyar, R.Wallis, J.Mollenhauer, and U.Holmskov (2010).
The recognition unit of FIBCD1 organizes into a noncovalently linked tetrameric structure and uses a hydrophobic funnel (S1) for acetyl group recognition.
  J Biol Chem, 285, 1229-1238.  
19710151 J.Whidby, G.Mateu, H.Scarborough, B.Demeler, A.Grakoui, and J.Marcotrigiano (2009).
Blocking hepatitis C virus infection with recombinant form of envelope protein 2 ectodomain.
  J Virol, 83, 11078-11089.  
17322526 K.B.Pabbisetty, X.Yue, C.Li, J.P.Himanen, R.Zhou, D.B.Nikolov, and L.Hu (2007).
Kinetic analysis of the binding of monomeric and dimeric ephrins to Eph receptors: correlation to function in a growth cone collapse assay.
  Protein Sci, 16, 355-361.  
17148457 M.Tanio, S.Kondo, S.Sugio, and T.Kohno (2007).
Trivalent recognition unit of innate immunity system: crystal structure of trimeric human M-ficolin fibrinogen-like domain.
  J Biol Chem, 282, 3889-3895.
PDB code: 2d39
  16820685 M.Tanio, S.Kondo, S.Sugio, and T.Kohno (2006).
Overexpression, purification and preliminary crystallographic analysis of human M-ficolin fibrinogen-like domain.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 652-655.  
16645151 N.P.Brindle, P.Saharinen, and K.Alitalo (2006).
Signaling and functions of angiopoietin-1 in vascular protection.
  Circ Res, 98, 1014-1023.  
16732286 W.A.Barton, D.Tzvetkova-Robev, E.P.Miranda, M.V.Kolev, K.R.Rajashankar, J.P.Himanen, and D.B.Nikolov (2006).
Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex.
  Nat Struct Mol Biol, 13, 524-532.
PDB codes: 2gy5 2gy7
16379598 S.G.Rockson (2005).
Literature watch. A genetic Xenopus laevis tadpole model to study lymphangiogenesis.
  Lymphat Res Biol, 3, 263-267.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.