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PDBsum entry 3bt1
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protein ligands Protein-protein interface(s) links
Immune system PDB id
3bt1

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
125 a.a. *
40 a.a. *
273 a.a. *
Ligands
NAG-NAG-MAN
NAG ×2
* Residue conservation analysis
PDB id:
3bt1
Name: Immune system
Title: Structure of urokinase receptor, urokinase and vitronectin complex
Structure: Urokinase-type plasminogen activator. Chain: a. Fragment: urokinase amino terminal fragment, urokinase-type plasminogen activator long chain a, unp residues 21-153. Synonym: upa, u-plasminogen activator. Engineered: yes. Vitronectin. Chain: b. Fragment: sometomedin-b domain.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: plau. Expressed in: drosophila melanogaster. Expression_system_taxid: 7227. Gene: vtn. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Resolution:
2.80Å     R-factor:   0.244     R-free:   0.308
Authors: M.Huang
Key ref:
Q.Huai et al. (2008). Crystal structures of two human vitronectin, urokinase and urokinase receptor complexes. Nat Struct Mol Biol, 15, 422-423. PubMed id: 18376415 DOI: 10.1038/nsmb.1404
Date:
27-Dec-07     Release date:   25-Mar-08    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00749  (UROK_HUMAN) -  Urokinase-type plasminogen activator from Homo sapiens
Seq:
Struc: 		431 a.a.
125 a.a.*
Protein chain
Pfam   ArchSchema ?
P04004  (VTNC_HUMAN) -  Vitronectin from Homo sapiens
Seq:
Struc: 		478 a.a.
40 a.a.
Protein chain
Pfam   ArchSchema ?
Q03405  (UPAR_HUMAN) -  Urokinase plasminogen activator surface receptor from Homo sapiens
Seq:
Struc: 		335 a.a.
273 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chain A: E.C.3.4.21.73  - u-plasminogen activator.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.

 

 
DOI no: 10.1038/nsmb.1404 Nat Struct Mol Biol 15:422-423 (2008)
PubMed id: 18376415  
 
 
Crystal structures of two human vitronectin, urokinase and urokinase receptor complexes.
Q.Huai, A.Zhou, L.Lin, A.P.Mazar, G.C.Parry, J.Callahan, D.E.Shaw, B.Furie, B.C.Furie, M.Huang.
 
  ABSTRACT  
 
The urokinase receptor (uPAR) can recognize several ligands. The structural basis for this multiple ligand recognition by uPAR is unknown. This study reports the crystal structures of uPAR in complex with both urokinase (uPA) and vitronectin and reveal that uPA occupies the central cavity of the receptor, whereas vitronectin binds at the outer side of the receptor. These results provide a structural understanding of one receptor binding to two ligands.
 
  Selected figure(s)  
 
Figure 1.
Stereoview of superimposed crystal structures of the uPAR–ATF–SMB complex and the uPAR–ATF–SMB-antibody complex are shown (the antibody is omitted for clarity). The carbohydrate moieties of uPAR are shown in sticks. The three domains of uPAR are colored differently. 		Figure 2.
(a) Interaction of the vitronectin SMB domain with uPAR D1 (orange) and D2 domains (magenta) in stereoview. Selected contacting residues in ball-and-stick representation; hydrogen bonds are shown in dashed lines. (b) Residues Phe13, Tyr28 and Asp22 of vitronectin (in ribbon and transparent surface representation) form an open pocket to bind Arg91 of uPAR (in ribbon and stick). Tyr27 and Tyr28 of the SMB domain insert into a large cavity of uPAR, showing shape complementarity of this interface.
 
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: Nat Struct Mol Biol (2008, 15, 422-423) copyright 2008.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21240271 J.Hausmann, S.Kamtekar, E.Christodoulou, J.E.Day, T.Wu, Z.Fulkerson, H.M.Albers, L.A.van Meeteren, A.J.Houben, L.van Zeijl, S.Jansen, M.Andries, T.Hall, L.E.Pegg, T.E.Benson, M.Kasiem, K.Harlos, C.W.Kooi, S.S.Smyth, H.Ovaa, M.Bollen, A.J.Morris, W.H.Moolenaar, and A.Perrakis (2011).
Structural basis of substrate discrimination and integrin binding by autotaxin.
  Nat Struct Mol Biol, 18, 198-204.
PDB codes: 2xr9 2xrg
21454081 M.De Souza, H.Matthews, J.A.Lee, M.Ranson, and M.J.Kelso (2011).
Small molecule antagonists of the urokinase (uPA): urokinase receptor (uPAR) interaction with high reported potencies show only weak effects in cell-based competition assays employing the native uPAR ligand.
  Bioorg Med Chem, 19, 2549-2556.  
20027185 H.W.Smith, and C.J.Marshall (2010).
Regulation of cell signalling by uPAR.
  Nat Rev Mol Cell Biol, 11, 23-36.  
20195466 I.M.Francischetti, M.Kotsyfakis, J.F.Andersen, and J.Lukszo (2010).
Cyr61/CCN1 displays high-affinity binding to the somatomedin B(1-44) domain of vitronectin.
  PLoS One, 5, e9356.  
20133942 L.Lin, H.Gårdsvoll, Q.Huai, M.Huang, and M.Ploug (2010).
Structure-based engineering of species selectivity in the interaction between urokinase and its receptor: implication for preclinical cancer therapy.
  J Biol Chem, 285, 10982-10992.
PDB code: 3laq
  20927316 S.A.Rabbani, B.Ateeq, A.Arakelian, M.L.Valentino, D.E.Shaw, L.M.Dauffenbach, C.A.Kerfoot, and A.P.Mazar (2010).
An anti-urokinase plasminogen activator receptor antibody (ATN-658) blocks prostate cancer invasion, migration, growth, and experimental skeletal metastasis in vitro and in vivo.
  Neoplasia, 12, 778-788.  
19668868 C.W.Ko, Z.Wei, R.J.Marsh, D.A.Armoogum, N.Nicolaou, A.J.Bain, A.Zhou, and L.Ying (2009).
Probing nanosecond motions of plasminogen activator inhibitor-1 by time-resolved fluorescence anisotropy.
  Mol Biosyst, 5, 1025-1031.  
19017261 D.C.Rijken, and H.R.Lijnen (2009).
New insights into the molecular mechanisms of the fibrinolytic system.
  J Thromb Haemost, 7, 4.  
19383607 V.D'mello, S.Singh, Y.Wu, and R.B.Birge (2009).
The urokinase plasminogen activator receptor promotes efferocytosis of apoptotic cells.
  J Biol Chem, 284, 17030-17038.  
20025562 Z.Chen, L.Lin, Q.Huai, and M.Huang (2009).
Challenges for drug discovery - a case study of urokinase receptor inhibition.
  Comb Chem High Throughput Screen, 12, 961-967.  
18718938 B.Royer-Zemmour, M.Ponsole-Lenfant, H.Gara, P.Roll, C.Lévêque, A.Massacrier, G.Ferracci, J.Cillario, A.Robaglia-Schlupp, R.Vincentelli, P.Cau, and P.Szepetowski (2008).
Epileptic and developmental disorders of the speech cortex: ligand/receptor interaction of wild-type and mutant SRPX2 with the plasminogen activator receptor uPAR.
  Hum Mol Genet, 17, 3617-3630.  
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 codes are shown on the right.

 

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