Stabilizing a flexible interdomain hinge region harboring the SMB binding site drives upar into its closed conformation

Journal of Molecular Biology

Volumn 427, Issue 6, 2015, Pages 1389-1403

  Zhao, Baoyu ^a,e   Gandhi, Sonu ^b   Yuan, Cai ^a,e   Luo, Zhipu ^a,e   Li, Rui ^a,d   Gårdsvoll, Henrik ^c,d,e   De Lorenzi, Valentina ^b   Sidenius, Nicolai ^b   Huang, Mingdong ^a,e   Ploug, Michael ^c,d,e  

^a FUJIAN INSTITUTE OF RESEARCH ON THE STRUCTURE OF MATTER   (China)

^b FIRC INSTITUTE OF MOLECULAR ONCOLOGY   (Italy)

^c FINSEN LABORATORY   (Denmark)

^d UNIVERSITY OF COPENHAGEN   (Denmark)

^e Danish Chinese Centre for Proteases Cancer   (Denmark)

Author keywords

allosteric regulati; CD87; LU domains; surface plasmon resonance; urokinase

Indexed keywords

ARGININE; EPITOPE; LIGAND; MONOCLONAL ANTIBODY; SOMATOMEDIN B; UROKINASE; UROKINASE RECEPTOR; VITRONECTIN; SOMATOMEDIN;

ARTICLE; BINDING AFFINITY; BINDING KINETICS; BINDING SITE; CELL MIGRATION; COMPLEX FORMATION; CONTROLLED STUDY; CRYSTAL STRUCTURE; EPITOPE MAPPING; EXTRACELLULAR MATRIX; HEK293 CELL LINE; HINGE REGION; HUMAN; HUMAN CELL; HYDROPHOBICITY; LAMELLIPODIUM; MOLECULAR DYNAMICS; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN STABILITY; PROTEIN STRUCTURE; SURFACE PLASMON RESONANCE; AMINO ACID SEQUENCE; CELL ADHESION; CHEMICAL STRUCTURE; CHEMISTRY; IMMUNOLOGY; KINETICS; METABOLISM; MOLECULAR GENETICS; PROTEIN TERTIARY STRUCTURE; PSEUDOPODIUM; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION; X RAY CRYSTALLOGRAPHY;

AMINO ACID SEQUENCE; ANTIBODIES, MONOCLONAL; BINDING SITES; CELL ADHESION; CRYSTALLOGRAPHY, X-RAY; EPITOPE MAPPING; HUMANS; KINETICS; LIGANDS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; PSEUDOPODIA; RECEPTORS, UROKINASE PLASMINOGEN ACTIVATOR; SEQUENCE HOMOLOGY, AMINO ACID; SIGNAL TRANSDUCTION; SOMATOMEDINS; SURFACE PLASMON RESONANCE; UROKINASE-TYPE PLASMINOGEN ACTIVATOR; VITRONECTIN;

EID: 84924163857     PISSN: 00222836     EISSN: 10898638     Source Type: Journal    
DOI: 10.1016/j.jmb.2015.01.022     Document Type: Article

References (63)

1. M. Ploug, E. Rønne, N. Behrendt, A.L. Jensen, F. Blasi, and K. Danø Cellular receptor for urokinase plasminogen activator. Carboxyl-terminal processing and membrane anchoring by glycosyl-phosphatidylinositol J Biol Chem 266 1991 1926 1933
2. H.W. Smith, and C.J. Marshall Regulation of cell signalling by uPAR Nat Rev Mol Cell Biol 11 2010 23 36
3. X. Xu, H. Gårdsvoll, C. Yuan, L. Lin, M. Ploug, and M. Huang Crystal structure of the urokinase receptor in a ligand-free form J Mol Biol 416 2012 629 641
4. L. Lin, H. Gårdsvoll, Q. Huai, M. Huang, and M. Ploug Structure-based engineering of species selectivity in the interaction between urokinase and its receptor: implication for preclinical cancer therapy J Biol Chem 285 2010 10982 10992
5. Q. Huai, A.P. Mazar, A. Kuo, G.C. Parry, D.E. Shaw, and J. Callahan Structure of human urokinase plasminogen activator in complex with its receptor Science 311 2006 656 659
6. Q. Huai, A. Zhou, L. Lin, A.P. Mazar, G.C. Parry, and J. Callahan Crystal structures of two human vitronectin, urokinase and urokinase receptor complexes Nat Struct Mol Biol 15 2008 422 423
7. P. Llinas, M.H. Le Du, H. Gårdsvoll, K. Danø, M. Ploug, and B. Gilquin Crystal structure of the human urokinase plasminogen activator receptor bound to an antagonist peptide EMBO J 24 2005 1655 1663
8. C. Barinka, G. Parry, J. Callahan, D.E. Shaw, A. Kuo, and K. Bdeir Structural basis of interaction between urokinase-type plasminogen activator and its receptor J Mol Biol 363 2006 482 495
9. H. Gårdsvoll, B. Gilquin, M.H. Le Du, A. Menez, T.J. Jørgensen, and M. Ploug Characterization of the functional epitope on the urokinase receptor. Complete alanine scanning mutagenesis supplemented by chemical cross-linking J Biol Chem 281 2006 19260 19272
10. H. Gårdsvoll, and M. Ploug Mapping of the vitronectin-binding site on the urokinase receptor: involvement of a coherent receptor interface consisting of residues from both domain I and the flanking interdomain linker region J Biol Chem 282 2007 13561 13572
11. V. Ellis, and K. Dano Potentiation of plasminogen activation by an anti-urokinase monoclonal antibody due to ternary complex formation. A mechanistic model for receptor-mediated plasminogen activation J Biol Chem 268 1993 4806 4813
12. M. Khanna, F. Wang, I. Jo, W.E. Knabe, S.M. Wilson, and L. Li Targeting multiple conformations leads to small molecule inhibitors of the uPAR·uPA protein-protein interaction that block cancer cell invasion ACS Chem Biol 6 2011 1232 1243
13. H. Gårdsvoll, B. Jacobsen, M.C. Kriegbaum, N. Behrendt, L. Engelholm, and S. stergaard Conformational regulation of urokinase receptor function: impact of receptor occupancy and epitope-mapped monoclonal antibodies on lamellipodia induction J Biol Chem 286 2011 33544 33556
14. C.D. Madsen, G.M. Ferraris, A. Andolfo, O. Cunningham, and N. Sidenius uPAR-induced cell adhesion and migration: vitronectin provides the key J Cell Biol 177 2007 927 939
15. D.A. Waltz, and H.A. Chapman Reversible cellular adhesion to vitronectin linked to urokinase receptor occupancy J Biol Chem 269 1994 14746 14750
16. S.M. Kanse, C. Kost, O.G. Wilhelm, P.A. Andreasen, and K.T. Preissner The urokinase receptor is a major vitronectin-binding protein on endothelial cells Exp Cell Res 224 1996 344 353
17. R.M. Salasznyk, M. Zappala, M. Zheng, L. Yu, C. Wilkins-Port, and P.J. McKeown-Longo The uPA receptor and the somatomedin B region of vitronectin direct the localization of uPA to focal adhesions in microvessel endothelial cells Matrix Biol 26 2007 359 370
18. V. Pirazzoli, G.M. Ferraris, and N. Sidenius Direct evidence of the importance of vitronectin and its interaction with the urokinase receptor in tumor growth Blood 121 2013 2316 2323
19. B.M. Connolly, E.Y. Choi, H. Gårdsvoll, A.L. Bey, B.M. Currie, and T. Chavakis Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation Blood 116 2010 1593 1603
20. C. Wei, C.C. Moller, M.M. Altintas, J. Li, K. Schwarz, and S. Zacchigna Modification of kidney barrier function by the urokinase receptor Nat Med 14 2008 55 63
21. A. Jögi, J. Pass, G. Høyer-Hansen, L.R. Lund, B.S. Nielsen, and K. Danø Systemic administration of anti-urokinase plasminogen activator receptor monoclonal antibodies induces hepatic fibrin deposition in tissue-type plasminogen activator deficient mice J Thromb Haemost 5 2007 1936 1944
22. H.M. Zhou, A. Nichols, P. Meda, and J.D. Vassalli Urokinase-type plasminogen activator and its receptor synergize to promote pathogenic proteolysis EMBO J 19 2000 4817 4826
23. T. Mani, F. Wang, W.E. Knabe, A.L. Sinn, M. Khanna, and I. Jo Small-molecule inhibition of the uPAR.uPA interaction: synthesis, biochemical, cellular, in vivo pharmacokinetics and efficacy studies in breast cancer metastasis Bioorg Med Chem 21 2013 2145 2155
24. H. Gårdsvoll, M. Kjaergaard, B. Jacobsen, M.C. Kriegbaum, M. Huang, and M. Ploug Mimicry of the regulatory role of urokinase in lamellipodia formation by introduction of a non-native interdomain disulfide bond in its receptor J Biol Chem 286 2011 43515 43526
25. D.I. Leavesley, A.S. Kashyap, T. Croll, M. Sivaramakrishnan, A. Shokoohmand, and B.G. Hollier Vitronectin - master controller or micromanager? IUBMB Life 65 2013 807 818
26. A. Stockmann, S. Hess, P. Declerck, R. Timpl, and K.T. Preissner Multimeric vitronectin. Identification and characterization of conformation-dependent self-association of the adhesive protein J Biol Chem 268 1993 22874 22882
27. A. Stahl, and B.M. Mueller The urokinase-type plasminogen activator receptor, a GPI-linked protein, is localized in caveolae J Cell Biol 129 1995 335 344
28. O. Cunningham, A. Andolfo, M.L. Santovito, L. Iuzzolino, F. Blasi, and N. Sidenius Dimerization controls the lipid raft partitioning of uPAR/CD87 and regulates its biological functions EMBO J 22 2003 5994 6003
29. H.D. Mertens, M. Kjaergaard, S. Mysling, H. Gårdsvoll, T.J. Jørgensen, and D.I. Svergun A flexible multidomain structure drives the function of the urokinase-type plasminogen activator receptor (uPAR) J Biol Chem 287 2012 34304 34315
30. T. Mizushima, T. Sugimoto, T. Kasumi, K. Araki, H. Kobayashi, and N. Kurita Ab initio molecular simulations for proposing novel peptide inhibitors blocking the ligand-binding pocket of urokinase receptor J Mol Model 20 2014 2292
31. V.E. Rea, A. Lavecchia, C. Di Giovanni, F.W. Rossi, A. Gorrasi, and A. Pesapane Discovery of new small molecules targeting the vitronectin-binding site of the urokinase receptor that block cancer cell invasion Mol Cancer Ther 12 2013 1402 1416
32. G. Sowmya, J.M. Khan, S. Anand, S.B. Ahn, M.S. Baker, and S. Ranganathan A site for direct integrin alphavbeta6·uPAR interaction from structural modelling and docking J Struct Biol 185 2014 327 335
33. Y. Li, G. Parry, L. Chen, J.A. Callahan, D.E. Shaw, and E.J. Meehan An anti-urokinase plasminogen activator receptor (uPAR) antibody: crystal structure and binding epitope J Mol Biol 365 2007 1117 1129
34. Sidenius N, Gandhi S. Constitutively active uPAR variants and their use for the generation and isolation of inhibitory antibodies. WO 2013/020898 A12013. pp. 1-99.
35. M. Ploug Structure-driven design of radionuclide tracers for non-invasive imaging of uPAR and targeted radiotherapy. The tale of a synthetic peptide antagonist Theranostics 3 2013 467 476
36. M. Persson, M. Hosseini, J. Madsen, T.J. Jørgensen, K.J. Jensen, and A. Kjaer Improved PET imaging of uPAR expression using new (64)Cu-labeled cross-bridged peptide ligands: comparative in vitro and in vivo studies Theranostics 3 2013 618 632
37. A. Zhou, J.A. Huntington, N.S. Pannu, R.W. Carrell, and R.J. Read How vitronectin binds PAI-1 to modulate fibrinolysis and cell migration Nat Struct Biol 10 2003 541 544
38. L.E. Odekon, Y. Sato, and D.B. Rifkin Urokinase-type plasminogen activator mediates basic fibroblast growth factor-induced bovine endothelial cell migration independent of its proteolytic activity J Cell Physiol 150 1992 258 263
39. N. Busso, S.K. Masur, D. Lazega, S. Waxman, and L. Ossowski Induction of cell migration by pro-urokinase binding to its receptor: possible mechanism for signal transduction in human epithelial cells J Cell Biol 126 1994 259 270
40. V. Ellis, N. Behrendt, and K. Danø Plasminogen activation by receptor-bound urokinase. A kinetic study with both cell-associated and isolated receptor J Biol Chem 266 1991 12752 12758
41. R. Hildenbrand, M. Niedergethmann, A. Marx, D. Belharazem, H. Allgayer, and C. Schleger Amplification of the urokinase-type plasminogen activator receptor (uPAR) gene in ductal pancreatic carcinomas identifies a clinically high-risk group Am J Pathol 174 2009 2246 2253
42. S. Serrati, F. Margheri, A. Chilla, E. Neumann, U. Muller-Ladner, and M. Benucci Reduction of in vitro invasion and in vivo cartilage degradation in a SCID mouse model by loss of function of the fibrinolytic system of rheumatoid arthritis synovial fibroblasts Arthritis Rheum 63 2011 2584 2594
43. N. Seeds, S. Mikesell, R. Vest, T. Bugge, K. Schaller, and K. Minor Plasminogen activator promotes recovery following spinal cord injury Cell Mol Neurobiol 31 2011 961 967
44. B. Meijers, R. Poesen, K. Claes, R. Dietrich, B. Bammens, and B. Sprangers Soluble urokinase receptor is a biomarker of cardiovascular disease in chronic kidney disease Kidney Int 87 2014 210 216.
45. M. Hoenigl, R.B. Raggam, J. Wagner, T. Valentin, E. Leitner, and K. Seeber Diagnostic accuracy of soluble urokinase plasminogen activator receptor (suPAR) for prediction of bacteremia in patients with systemic inflammatory response syndrome Clin Biochem 46 2013 225 229
46. I.K. Lund, M. Illemann, T. Thurison, I.J. Christensen, and G. Høyer-Hansen uPAR as anti-cancer target: evaluation of biomarker potential, histological localization, and antibody-based therapy Curr Drug Targets 12 2011 1744 1760
47. T. Thurison, A.F. Lomholt, M.G. Rasch, I.K. Lund, H.J. Nielsen, and I.J. Christensen A new assay for measurement of the liberated domain I of the urokinase receptor in plasma improves the prediction of survival in colorectal cancer Clin Chem 56 2010 1636 1640
48. T. Piironen, B. Laursen, J. Pass, K. List, H. Gårdsvoll, and M. Ploug Specific immunoassays for detection of intact and cleaved forms of the urokinase receptor Clin Chem 50 2004 2059 2068
49. Y. Su, J. Ortiz, S. Liu, T.H. Bugge, R. Singh, and S.H. Leppla Systematic urokinase-activated anthrax toxin therapy produces regressions of subcutaneous human non-small cell lung tumor in athymic nude mice Cancer Res 67 2007 3329 3336
50. M. Ploug, S. stergaard, H. Gårdsvoll, K. Kovalski, C. Holst-Hansen, and A. Holm 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 2001 12157 12168
51. M. Persson, K. Juhl, P. Rasmussen, M. Brandt-Larsen, J. Madsen, and M. Ploug uPAR targeted radionuclide therapy with 177Lu-DOTA-AE105 inhibits dissemination of metastatic prostate cancer Mol Pharm 11 2014 2796 2806
52. A.M. LeBeau, S. Duriseti, S.T. Murphy, F. Pepin, B. Hann, and J.W. Gray Targeting uPAR with antagonistic recombinant human antibodies in aggressive breast cancer Cancer Res 73 2013 2070 2081
53. T.W. Bauer, W. Liu, F. Fan, E.R. Camp, A. Yang, and R.J. Somcio Targeting of urokinase plasminogen activator receptor in human pancreatic carcinoma cells inhibits c-Met- and insulin-like growth factor-I receptor-mediated migration and invasion and orthotopic tumor growth in mice Cancer Res 65 2005 7775 7781
54. M. Resnati, I. Pallavicini, J.M. Wang, J. Oppenheim, C.N. Serhan, and M. Romano The fibrinolytic receptor for urokinase activates the G protein-coupled chemotactic receptor FPRL1/LXA4R Proc Natl Acad Sci U S A 99 2002 1359 1364
55. M. Resnati, M. Guttinger, S. Valcamonica, N. Sidenius, F. Blasi, and F. Fazioli Proteolytic cleavage of the urokinase receptor substitutes for the agonist-induced chemotactic effect EMBO J 15 1996 1572 1582
56. F. Fazioli, M. Resnati, N. Sidenius, Y. Higashimoto, E. Appella, and F. Blasi A urokinase-sensitive region of the human urokinase receptor is responsible for its chemotactic activity EMBO J 16 1997 7279 7286
57. X. Xu, Y. Cai, Y. Wei, F. Donate, J. Juarez, and G. Parry Identification of a new epitope in uPAR as a target for the cancer therapeutic monoclonal antibody ATN-658, a structural homolog of the uPAR binding integrin CD11b (alphaM) PLoS One 9 2014 e85349
58. M. Freeman, C. Klambt, C.S. Goodman, and G.M. Rubin The argos gene encodes a diffusible factor that regulates cell fate decisions in the Drosophila eye Cell 69 1992 963 975
59. D.E. Klein, V.M. Nappi, G.T. Reeves, S.Y. Shvartsman, and M.A. Lemmon Argos inhibits epidermal growth factor receptor signalling by ligand sequestration Nature 430 2004 1040 1044
60. D.E. Klein, S.E. Stayrook, F. Shi, K. Narayan, and M.A. Lemmon Structural basis for EGFR ligand sequestration by Argos Nature 453 2008 1271 1275
61. H. Gårdsvoll, F. Werner, L. Søndergaard, K. Danø, and M. Ploug 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 2004 284 295
62. B. Jacobsen, H. Gårdsvoll, G. Juhl Funch, S. stergaard, V. Barkholt, and M. Ploug One-step affinity purification of recombinant urokinase-type plasminogen activator receptor using a synthetic peptide developed by combinatorial chemistry Protein Expr Purif 52 2007 286 296
63. M. Kjaergaard, H. Gårdsvoll, D. Hirschberg, S. Nielbo, A. Mayasundari, and C.B. Peterson Solution structure of recombinant somatomedin B domain from vitronectin produced in Pichia pastoris Protein Sci 16 2007 1934 1945