Crystal structure of the human urokinase plasminogen activator receptor bound to an antagonist peptide

EMBO Journal

Volumn 24, Issue 9, 2005, Pages 1655-1663

  Llinas, Paola ^a   Le Du, Marie Hélène ^a   Gårdswoll, Henrik ^b   Danø, Keld ^b   Ploug, Michael ^b   Gilquin, Bernard ^a   Stura, Enrico A ^a   Ménez, André ^a  

^a DIF   (France)

^b FINSEN LABORATORY   (Denmark)

Author keywords

Cancer; Structure; Three finger fold; Tissue remodelling; uPAR

Indexed keywords

INTEGRIN; RECEPTOR BLOCKING AGENT; UROKINASE RECEPTOR; VITRONECTIN;

AMINO ACID SEQUENCE; ARTICLE; BINDING AFFINITY; CELL SURFACE; CONTROLLED STUDY; CRYSTAL STRUCTURE; CRYSTALLIZATION; MICROENVIRONMENT; NONHUMAN; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; RECEPTOR BINDING; STROMA CELL;

CRYSTALLIZATION; HUMANS; MOLECULAR CONFORMATION; PEPTIDES; PROTEIN BINDING; RECEPTORS, CELL SURFACE; RECOMBINANT PROTEINS; URINARY PLASMINOGEN ACTIVATOR;

EID: 18944401136     PISSN: 02614189     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.emboj.7600635     Document Type: Article

References (60)

1. Appella E, Robinson EA, Ullrich SJ, Stoppelli MP, Corti A, Cassani G, Blasi F (1987) The receptor-binding sequence of urokinase. A biological function for the growth-factor module of proteases. J Biol Chem 262: 4437-4440
2. Bdeir K, Kuo A, Mazar A, Sachais BS, Xiao W, Gawlak S, Harris S, Higazi AA, Cines DB (2000) A region in domain II of the urokinase receptor required for urokinase binding. J Biol Chem. 275: 28532-28538
3. Blasi F, Carmeliet P (2002) uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol 3: 932-943
4. Bolon I, Zhou HM, Charron Y, Wohlwend A, Vassalli JD (2004) Plasminogen mediates the pathological effects of urokinase-type plasminogen activator overexpression. Am J Pathol 164: 2299-2304
5. Brooks BR, Karplus M, Petit BM (1988) Proteins: A Theoretical Perspective of Dynamics, Structure and Thermodynamics. New York: Wiley
6. Cunningham O, Andolfo A, Santovito ML, Iuzzolino L, Blasi F, Sidenius N (2003) Dimerization controls the lipid raft partitioning of uPAR/CD87 and regulates its biological functions. EMBO J 22: 5994-6003
7. De La Fortelle E, Bricogne G (1997) Maximum-likelihood heavy-atom parameter refinement for multiple isomorphous replacement and multiwavelength anomalous diffraction methods. Methods Enzymol 276: 472-493
8. Deng G, Curriden SA, Wang S, Rosenberg S, Loskutoff DJ (1996) Is plasminogen activator inhibitor-1 the molecular switch that governs urokinase receptor-mediated cell adhesion and release? J Cell Biol 134: 1563-1571
9. Ellis V, Scully MF, Kakkar W (1989) Plasminogen activation initiated by single-chain urokinase-type plasminogen activator. Potentiation by U937 monocytes. J Biol Chem. 264: 2185-2188
10. Engelholm LH, Behrendt N (2001) Differential binding of urokinase and peptide antagonists to the urokinase receptor: evidence from characterization of the receptor in four primate species. Biol Chem 382: 435-442
11. Eriksson MA, Roux B (2002) Modeling the structure of agitoxin in complex with the Shaker K + channel: a computational approach based on experimental distance restraints extracted from thermodynamic mutant cycles. Biophys J 83: 2595-2609
12. Estreicher A, Wohlwend A, Belin D, Schleuning WD, Vassalli JD (1989) Characterization of the cellular binding site for the urokinase-type plasminogen activator. J Biol Chem 264: 1180-1189
13. Fazioli F, Resnati M, Sidenius N, Higashimoto Y, Appella E, Blasi F (1997) A urokinase-sensitive region of the human urokinase receptor is responsible for its chemotactic activity. EMBO J 16: 7279-7286
14. Fletcher CM, Harrison RA, Lachmann PJ, Neuhaus D (1994) Structure of a soluble, glycosylated form of the human complement regulatory protein CD59. Structure 2: 185-199
15. Fowler B, Mackman N, Parmer RJ, Miles LA (1998) Binding of human single chain urokinase to Chinese hamster ovary cells and cloning of hamster u-PAR. Thromb Haemostasis 80: 148-154
16. Gårdsvoll H, Danø K, Ploug M (1999) Mapping part of the functional epitope for ligand binding on the receptor for urokinase-type plasminogen activator by site-directed mutagenesis. J Biol Chem. 274: 37995-38003
17. Gårdsvoll H, Werner F, Søndergaard L, Danø K, Ploug M (2004) Characterization of low-glycosylated forms of soluble human urokinase receptor expressed in Drosophila Schneider 2 cells after deletion of glycosylation-sites. Protein Expr Purif 34: 284-295
18. Goodson RJ, Doyle MV, Kaufman SE, Rosenberg S (1994) High-affinity urokinase receptor antagonists identified with bacteriophage peptide display. Proc Natl Acad Sci USA 91: 7129-7133
19. Greenwald J, Fischer WH, Vale WW, Choe S (1999) Three-finger toxin fold for the extracellular ligand-binding domain of the type II activin receptor serine kinase. Nat Struct Biol 6: 18-22
20. Hansen AP, Petros AM, Meadows RP, Nettesheim DG, Mazar AP, Olejniczak ET, Xu RX, Pederson TM, Henkin J, Fesik SW (1994) Solution structure of the amino-terminal fragment of urokinase-type plasminogen activator. Biochemistry 33: 4847-4864
21. Hansen LV, Gårdsvoll H, Nielsen BS, Lund LR, Danø K, Jensen ON, Ploug M (2004) Structural analysis and tissue localization of human C4.4A: a protein homologue of the urokinase receptor. Biochem J 380: 845-857
22. Hart PJ, Deep S, Taylor AB, Shu Z, Hinck CS, Hinck AP (2002) Crystal structure of the human TbetaR2 ectodomain-TGF-beta3 complex. Nat Struct Biol 9: 203-208
23. Heiss MM, Allgayer H, Gruetzner KU, Funke I, Babic R, Jauch KW, Schildberg FW (1995) Individual development and uPA-receptor expression of disseminated tumour cells in bone marrow: a reference to early systemic disease in solid cancer. Nat Med 1: 1035-1039
24. Jørgensen TJ, Gårdsvoll H, Danø K, Roepstorff P, Ploug M (2004) Dynamics of urokinase receptor interaction with peptide antagonists studied by amide hydrogen exchange and mass spectrometry. Biochemistry 43: 15044-15057
25. Kirsch T, Sebald W, Dreyer MK (2000) Crystal structure of the BMP-2-BRIA ectodomain complex. Nat Struct Biol 7: 492-496
26. Kristensen P, Eriksen J, Blasi F, Danø K (1991) Two alternatively spliced mouse urokinase receptor mRNAs with different histological localization in the gastrointestinal tract. J Cell Biol 115: 1763-1771
27. Li Y, Lawrence DA, Zhang L (2003) Sequences within domain II of the urokinase receptor critical for differential ligand recognition. J Biol Chem 278: 29925-29932
28. Lo Conte L, Chothia C, Janin J (1999) The atomic structure of protein-protein recognition sites. J Mol Biol 285: 2177-2198
29. Low BW, Preston HS, Sato A, Rosen LS, Searl JE, Rudko AD, Richardson JS (1976) Three dimensional structure of erabutoxin b neurotoxic protein: inhibitor of acetylcholine receptor. Proc Natl Acad Sci USA 73: 2991-2994
30. Lynn GW, Heller WT, Mayasundari A, Minor KH, Peterson CB (2005) A model for the three-dimensional structure of human plasma vitronectin from small-angle scattering measurements. Biochemistry 44: 565-574
31. MacKerell AD, Bashford D, Bellott RL, Dunbrack RL, Evanseck JD, Field MJ, Fischer S, Gao J, Guo H, Ha S, Joseph-McCarthy D, Kuchnir L, Kuczera K, Lau FTK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, Reiher WE, Roux B, Schlenkrich M, Smith JC, Stote R, Straub J, Watanabe M, Wiorkiewicz-Kuczera J, Yin D, Karplus M (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins. J Phys Chem B 102: 3586-3616
32. Magdolen V, Rettenberger P, Koppitz M, Goretzki L, Kessler H, Weidle UH, König B, Graeff H, Schmitt M, Wilhelm O (1996) Systematic mutational analysis of the receptor-binding region of the human urokinase-type plasminogen activator. Eur J Biochem 237: 743-751
33. Ménez A, Servent D, Gasparini S (2002) Perspective in Molecular Toxinology. Chichester: Wiley
34. Mustjoki S, Sidenius N, Sier CF, Blasi F, Elonen E, Alitalo R, Vaheri A (2000) Soluble urokinase receptor levels correlate with number of circulating tumor cells in acute myeloid leukemia and decrease rapidly during chemotherapy. Cancer Res 60: 7126-7132
35. Otwinowski Z, Minor W (1997) Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol 276: 307-326
36. Pappot H, Høyer-Hansen G, Rønne E, Hansen HH, Brünner N, Danø K, Grøndahl-Hansen J (1997) Elevated plasma levels of urokinase plasminogen activator receptor in non-small cell lung cancer patients. Eur J Cancer 33: 867-872
37. Ploug M (1998) Identification of specific sites involved in ligand binding by photoaffinity labeling of the receptor for the urokinase-type plasminogen activator. Residues located at equivalent positions in uPAR domains I and III participate in the assembly of a composite ligand-binding site. Biochemistry 37: 16494-16505
38. Ploug M (2003) Structure-function relationships in the interaction between the urokinase-type plasminogen activator and its receptor. Curr Pharm Des 9: 1499-1528
39. Ploug M, Ellis V (1994) Structure-function relationships in the receptor for urokinase-type plasminogen activator. Comparison to other members of the Ly-6 family and snake venom alpha-neurotoxins. FEBS Lett 349: 163-168
40. Ploug M, Kjalke M, Rønne E, Weidle U, Høyer-Hansen G, Danø K (1993) Localization of the disulfide bonds in the NH2-terminal domain of the cellular receptor for human urokinase-type plasminogen activator. A domain structure belonging to a novel superfamily of glycolipid-anchored membrane proteins. J Biol Chem 268: 17539-17546
41. Ploug M, Østergaard S, Gårdsvoll H, Kovalski K, Holst-Hansen C, Holm A, Ossowski L, Danø K (2001) Peptide-derived antagonists of the urokinase receptor. Affinity maturation by combinatorial chemistry, identification of functional epitopes, and inhibitory effect on cancer cell intravasation. Biochemistry 40: 12157-12168
42. Ploug M, Østergaard S, Hansen LB, Holm A, Danø K (1998) Photoaffinity labeling of the human receptor for urokinase-type plasminogen activator using a decapeptide antagonist. Evidence for a composite ligand-binding site and a short interdomain separation. Biochemistry 37: 3612-3622
43. Ploug M, Rahbek-Nielsen H, Ellis V, Roepstorff P, Danø K (1995) Chemical modification of the urokinase-type plasminogen activator and its receptor using tetranitromethane. Evidence for the involvement of specific tyrosine residues in both molecules during receptor-ligand interaction. Biochemistry 34: 12524-12534
44. Ploug M, Rønne E, Behrendt N, Jensen AL, Blasi F, Danø K (1991) Cellular receptor for urokinase plasminogen activator. Carboxyl-terminal processing and membrane anchoring by glycosyl-phosphatidylinositol. J Biol Chem. 266: 1926-1933
45. Pluskota E, Soloviev DA, Plow EF (2003) Convergence of the adhesive and fibrinolytic systems: recognition of urokinase by integrin alpha Mbeta 2 as well as by the urokinase receptor regulates cell adhesion and migration. Blood 101: 1582-1590
46. Roldan AL, Cubellis MV, Masucci MT, Behrendt N, Lund LR, Dano K, Appella E, Blasi F (1990) Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis. EMBO J 9: 467-474
47. Rømer J, Nielsen BS, Ploug M (2004) The urokinase receptor as a potential target in cancer therapy. Curr Pharm Des 10: 2359-2376
48. Rosenberg S (2001) New developments in the urokinase-type plasminogen activator system. Expert Opin Ther Targets 5: 711-722
49. Sato S, Kopitz C, Schmalix WA, Muehlenweg B, Kessler H, Schmitt M, Kruger A, Magdolen V (2002) High-affinity urokinase-derived cyclic peptides inhibiting urokinase/urokinase receptor-interaction: effects on tumor growth and spread. FEBS Lett 528: 212-216
50. Schmiedeberg N, Schmitt M, Rolz C, Truffault V, Sukopp M, Burgle M, Wilhelm OG, Schmalix W, Magdolen V, Kessler H (2002) Synthesis, solution structure, and biological evaluation of urokinase type plasminogen activator (uPA)-derived receptor binding domain mimetics. J Med Chem 45: 4984-4994
51. Stephens RW, Nielsen HJ, Christensen IJ, Thorlacius-Ussing O, Sørensen S, Danø K, Brünner N (1999) Plasma urokinase receptor levels in patients with colorectal cancer: relationship to prognosis. J Natl Cancer Inst 91: 869-874
52. Stura EA (1999) Seeding techniques. In Crystllization of Nucleic Acids and Proteins: A Practical Approach, Dueruix A and Giegé R (eds) 2nd edn. Oxford: Oxford University Press pp 177-208
53. Stura EA (2001) A simple modification of the Q-plate for parallel screening and combinatorial crystallization. J Cryst Growth 232: 545-552
54. Thompson TB, Woodruff TK, Jardetzky TS (2003) Structures of an ActRIIB:activin A complex reveal a novel binding mode for TGF-beta ligand:receptor interactions. EMBO J 22: 1555-1566
55. Torres AM, Kini RM, Selvanayagam N, Kuchel PW (2001) NMR structure of bucandin, a neurotoxin from the venom of the Malayan krait (Bungarus candidus). Biochem J 360: 539-548
56. Wei Y, Eble JA, Wang Z, Kreidberg JA, Chapman HA (2001) Urokinase receptors promote betal integrin function through interactions with integrin alpha3beta1. Mol Biol Cell 12: 2975-2986
57. Wei Y, Lukashev M, Simon DI, Bodary SC, Rosenberg S, Doyle MV, Chapman HA (1996) Regulation of integrin function by the urokinase receptor. Science 273: 1551-1555
58. Wei Y, Waltz DA, Rao N, Drummond RJ, Rosenberg S, Chapman HA (1994) Identification of the urokinase receptor as an adhesion receptor for vitronectin. J Biol Chem 269: 32380-32388
59. Zhou A, Huntington JA, Pannu NS, Carrell RW, Read RJ (2003) How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration. Nat Struct Biol 10: 541-544
60. Zhou HM, Nichols A, Meda P, Vassalli JD (2000) Urokinase-type plasminogen activator and its receptor synergize to promote pathogenic proteolysis. EMBO J 19: 4817-4826