An Anti-urokinase Plasminogen Activator Receptor (uPAR) Antibody: Crystal Structure and Binding Epitope

Journal of Molecular Biology

Volumn 365, Issue 4, 2007, Pages 1117-1129

  Li, Yongdong ^a,b   Parry, Graham ^c   Chen, Liqing ^d   Callahan, Jennifer A ^c   Shaw, David E ^e   Meehan, Edward J ^d   Mazar, Andrew P ^c   Huang, Mingdong ^a,b  

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

^b UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

^c Attenuon LLC   (United States)

^d UNIVERSITY OF ALABAMA IN HUNTSVILLE   (United States)

^e D E SHAW RESEARCH   (United States)

Author keywords

antibody; ATN615; crystal structure; Fab; uPAR

Indexed keywords

ARGININE; ASPARAGINE; EPITOPE; GLYCINE; IMMUNOGLOBULIN F(AB) FRAGMENT; MACROGOL; PROLINE; RECEPTOR ANTIBODY; UNCLASSIFIED DRUG; UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR ANTIBODY;

ANIMAL CELL; ANTIGEN ANTIBODY COMPLEX; ANTIGEN BINDING; ARTICLE; COMPLEMENTARITY DETERMINING REGION; CONTROLLED STUDY; CRYSTAL STRUCTURE; HUMAN; HUMAN CELL; IMMUNOCHEMISTRY; MOLECULAR INTERACTION; MOLECULAR RECOGNITION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; STRUCTURAL PROTEOMICS;

EID: 33845881968     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmb.2006.10.059     Document Type: Article

References (71)

1. Stoppelli M.P., Corti A., Soffientini A., Cassani G., Blasi F., and Assoian R.K. Differentiation-enhanced binding of the amino-terminal fragment of human urokinase plasminogen activator to a specific receptor on U937 monocytes. Proc. Natl Acad. Sci. USA 82 (1985) 4939-4943
2. Vassalli J.D., Baccino D., and Belin D. A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase. J. Cell Biol. 100 (1985) 86-92
3. Quigley J.P. Association of a protease (plasminogen activator) with a specific membrane fraction isolated from transformed cells. J. Cell Biol. 71 (1976) 472-486
4. Wei Y., Waltz D.A., Rao N., Drummond R.J., Rosenberg S., and Chapman H.A. Identification of the urokinase receptor as an adhesion receptor for vitronectin. J. Biol. Chem. 269 (1994) 32380-32388
5. Behrendt N. The urokinase receptor (uPAR) and the uPAR-associated protein (uPARAP/Endo180): membrane proteins engaged in matrix turnover during tissue remodeling. Biol. Chem. 385 (2004) 103-136
6. Resnati M., Guttinger M., Valcamonica S., Sidenius N., Blasi F., and Fazioli F. Proteolytic cleavage of the urokinase receptor substitutes for the agonist-induced chemotactic effect. EMBO J. 15 (1996) 1572-1582
7. Resnati M., Pallavicini I., Wang J.M., Oppenheim J., Serhan C.N., Romano M., and Blasi F. The fibrinolytic receptor for urokinase activates the G protein-coupled chemotactic receptor FPRL1/LXA4R. Proc. Natl Acad. Sci. USA 99 (2002) 1359-1364
8. Wei Y., Lukashev M., Simon D.I., Bodary S.C., Rosenberg S., Doyle M.V., and Chapman H.A. Regulation of integrin function by the urokinase receptor. Science 273 (1996) 1551-1555
9. Simon D.I., Wei Y., Zhang L., Rao N.K., Xu H., Chen Z., et al. Identification of a urokinase receptor-integrin interaction site. Promiscuous regulator of integrin function. J. Biol. Chem. 275 (2000) 10228-10234
10. Nguyen D.H., Catling A.D., Webb D.J., Sankovic M., Walker L.A., Somlyo A.V., et al. Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner. J. Cell Biol. 146 (1999) 149-164
11. Carriero M.V., Del Vecchio S., Capozzoli M., Franco P., Fontana L., Zannetti A., et al. Urokinase receptor interacts with alpha(v)beta5 vitronectin receptor, promoting urokinase-dependent cell migration in breast cancer. Cancer Res. 59 (1999) 5307-5314
12. Wei Y., Eble J.A., Wang Z., Kreidberg J.A., and Chapman H.A. Urokinase receptors promote beta1 integrin function through interactions with integrin alpha3beta1. Mol. Biol. Cell 12 (2001) 2975-2986
13. Aguirre Ghiso J.A., Alonso D.F., Farias E.F., Gomez D.E., and de Kier Joffe E.B. Deregulation of the signaling pathways controlling urokinase production. Its relationship with the invasive phenotype. Eur. J. Biochem. 263 (1999) 295-304
14. Blasi F., and Carmeliet P. uPAR: a versatile signalling orchestrator. Nature Rev. Mol. Cell. Biol. 3 (2002) 932-943
15. Kim J., Yu W., Kovalski K., and Ossowski L. Requirement for specific proteases in cancer cell intravasation as revealed by a novel semiquantitative PCR-based assay. Cell 94 (1998) 353-362
16. Ploug M. Structure-function relationships in the interaction between the urokinase-type plasminogen activator and its receptor. Curr. Pharm. Des. 9 (2003) 1499-1528
17. Stephens R.W., Nielsen H.J., Christensen I.J., Thorlacius-Ussing O., Sorensen S., Dano K., and Brunner N. Plasma urokinase receptor levels in patients with colorectal cancer: relationship to prognosis. J. Natl Cancer Inst. 91 (1999) 869-874
18. Ganesh S., Sier C.F., Heerding M.M., Griffioen G., Lamers C.B., and Verspaget H.W. Urokinase receptor and colorectal cancer survival. Lancet 344 (1994) 401-402
19. Riisbro R., Christensen I.J., Piironen T., Greenall M., Larsen B., Stephens R.W., et al. Prognostic significance of soluble urokinase plasminogen activator receptor in serum and cytosol of tumor tissue from patients with primary breast cancer. Clin. Cancer Res. 8 (2002) 1132-1141
20. Grondahl-Hansen J., Peters H.A., van Putten W.L., Look M.P., Pappot H., Ronne E., et al. Prognostic significance of the receptor for urokinase plasminogen activator in breast cancer. Clin. Cancer Res. 1 (1995) 1079-1087
21. Pappot H., Hoyer-Hansen G., Ronne E., Hansen H.H., Brunner N., Dano K., and Grondahl-Hansen J. Elevated plasma levels of urokinase plasminogen activator receptor in non-small cell lung cancer patients. Eur. J. Cancer 33 (1997) 867-872
22. Pedersen H., Brunner N., Francis D., Osterlind K., Ronne E., Hansen H.H., et al. Prognostic impact of urokinase, urokinase receptor, and type 1 plasminogen activator inhibitor in squamous and large cell lung cancer tissue. Cancer Res. 54 (1994) 4671-4675
23. Romer J., Nielsen B.S., and Ploug M. The urokinase receptor as a potential target in cancer therapy. Curr. Pharm. Des. 10 (2004) 2359-2376
24. Ploug M., Gardsvoll H., Jorgensen T.J., Lonborg Hansen L., and Dano K. Structural analysis of the interaction between urokinase-type plasminogen activator and its receptor: a potential target for anti-invasive cancer therapy. Biochem. Soc. Trans. 30 (2002) 177-183
25. Mazar A.P. The urokinase plasminogen activator receptor (uPAR) as a target for the diagnosis and therapy of cancer. Anticancer Drugs 12 (2001) 387-400
26. Bauer T.W., Liu W., Fan F., Camp E.R., Yang A., Somcio R.J., et al. 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
27. Rabbani S.A., and Gladu J. Urokinase receptor antibody can reduce tumor volume and detect the presence of occult tumor metastases in vivo. Cancer Res. 62 (2002) 2390-2397
28. Wilson I.A., and Stanfield R.L. Antibody-antigen interactions. Curr. Opin. Struct. Biol. 3 (1993) 113-118
29. Davies D.R., and Cohen G.H. Interactions of protein antigens with antibodies. Proc. Natl Acad. Sci. USA 93 (1996) 7-12
30. Huang M., Syed R., Stura E.A., Stone M.J., Stefanko R.S., Ruf W., et al. The mechanism of an inhibitory antibody on TF-initiated blood coagulation revealed by the crystal structures of human tissue factor, Fab 5G9 and TF, G9 complex. J. Mol. Biol. 275 (1998) 873-894
31. Jones S., and Thornton J.M. Principles of protein-protein interactions. Proc. Natl Acad. Sci. USA 93 (1996) 13-20
32. Collaborative Computational Project, Number 4. The CCP4 Suite: Programs for protein crystallography. Acta Crystallog. sect. D 50 (1994) 760-763
33. Huai Q., Mazar A.P., Kuo A., Parry G.C., Shaw D.E., Callahan J., et al. Structure of human urokinase plasminogen activator in complex with its receptor. Science 311 (2006) 656-659
34. Johnson G., and Wu T.T. Kabat Database and its applications: future directions. Nucl. Acids Res. 29 (2001) 205-206
35. Wilson I.A., and Stanfield R.L. Antibody-antigen interactions: new structures and new conformational changes. Curr. Opin. Struct. Biol. 4 (1994) 857-867
36. Liu D., Aguirre Ghiso J., Estrada Y., and Ossowski L. EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma. Cancer Cell 1 (2002) 445-457
37. Aguirre-Ghiso J.A., Estrada Y., Liu D., and Ossowski L. ERK(MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38(SAPK). Cancer Res. 63 (2003) 1684-1695
38. Aguirre-Ghiso J.A., Liu D., Mignatti A., Kovalski K., and Ossowski L. Urokinase receptor and fibronectin regulate the ERK(MAPK) to p38(MAPK) activity ratios that determine carcinoma cell proliferation or dormancy in vivo. Mol. Biol. Cell 12 (2001) 863-879
39. Kook Y.H., Adamski J., Zelent A., and Ossowski L. The effect of antisense inhibition of urokinase receptor in human squamous cell carcinoma on malignancy. EMBO J. 13 (1994) 3983-3991
40. Yu W., Kim J., and Ossowski L. Reduction in surface urokinase receptor forces malignant cells into a protracted state of dormancy. J. Cell Biol. 137 (1997) 767-777
41. Chaurasia P., Aguirre-Ghiso J.A., Liang O.D., Gardsvoll H., Ploug M., and Ossowski L. A region in urokinase plasminogen receptor domain III controlling a functional association with alpha5beta1 integrin and tumor growth. J. Biol. Chem. 281 (2006) 14852-14863
42. Liang O.D., Bdeir K., Matz R.L., Chavakis T., and Preissner K.T. Intermolecular contact regions in urokinase plasminogen activator receptor. J. Biochem. (Tokyo) 134 (2003) 661-666
43. Novotny J., Bruccoleri R.E., and Saul F.A. On the attribution of binding energy in antigen-antibody complexes McPC 603, D1.3, and HyHEL-5. Biochemistry 28 (1989) 4735-4749
44. Lawrence M.C., and Colman P.M. Shape complementarity at protein/protein interfaces. J. Mol. Biol. 234 (1993) 946-950
45. Bhat T.N., Bentley G.A., Boulot G., Greene M.I., Tello D., Dall'Acqua W., et al. Bound water molecules and conformational stabilization help mediate an antigen-antibody association. Proc. Natl Acad. Sci. USA 91 (1994) 1089-1093
46. Cohen G.H., Sheriff S., and Davies D.R. Refined structure of the monoclonal antibody HyHEL-5 with its antigen hen egg-white lysozyme. Acta Crystallog. sect. D 52 (1996) 315-326
47. Renault L., Kuhlmann J., Henkel A., and Wittinghofer A. Structural basis for guanine nucleotide exchange on Ran by the regulator of chromosome condensation (RCC1). Cell 105 (2001) 245-255
48. Mian I.S., Bradwell A.R., and Olson A.J. Structure, function and properties of antibody binding sites. J. Mol. Biol. 217 (1991) 133-151
49. Jirholt P., Strandberg L., Jansson B., Krambovitis E., Soderlind E., Borrebaeck C.A., et al. A central core structure in an antibody variable domain determines antigen specificity. Protein Eng. 14 (2001) 67-74
50. Stanfield R.L., Zemla A., Wilson I.A., and Rupp B. Antibody elbow angles are influenced by their light chain class. J. Mol. Biol. 357 (2006) 1566-1574
51. Llinas P., Le Du M.H., Gardsvoll H., Dano K., Ploug M., Gilquin B., et al. Crystal structure of the human urokinase plasminogen activator receptor bound to an antagonist peptide. EMBO J. 24 (2005) 1655-1663
52. Cai Yuan Q.H., Chuanbing B., and Mingdong H. The expression, purification and crystallization of monomeric soluble human urokinase receptor. Prog. Biochem. Biophys. 33 (2006) 277-281
53. Gardsvoll H., Werner F., Sondergaard L., Dano K., and Ploug M. 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
54. Li Y., Shi X., Parry G., Chen L., Callahan J.A., Mazar A.P., and Huang M. Optimization of crystals of an inhibitory antibody of urokinase plasminogen activator receptor (uPAR) with hydrogen peroxide and low protein concentration. Protein Pept. Letters 12 (2005) 655-658
55. Otwinowski Z.W. Minor. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276 (1997) 307-326
56. Navaza J. AMoRe: an automated package for molecular replacement. Acta Crystallog. sect. A 50 (1994) 157-163
57. Guex N., and Peitsch M.C. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18 (1997) 2714-2723
58. Brunger A.T., Adams P.D., Clore G.M., DeLano W.L., Gros P., Grosse-Kunstleve R.W., et al. Crystallography and NMR system: a new software suite for macromolecular structure determination. Acta Crystallog. sect. D 54 (1998) 905-921
59. Jones T.A., Zou J.Y., and Cowan S.W. Kjeldgaard. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallog. sect. A 47 (1991) 110-119
60. Martin A.C. Accessing the Kabat antibody sequence database by computer. Proteins: Struct. Funct. Genet. 25 (1996) 130-133
61. Tulip W.R., Varghese J.N., Webster R.G., Laver W.G., and Colman P.M. Crystal structures of two mutant neuraminidase-antibody complexes with amino acid substitutions in the interface. J Mol Biol 227 (1992) 149-159
62. Tulip W.R., Varghese J.N., Laver W.G., Webster R.G., and Colman P.M. Refined crystal structure of the influenza virus N9 neuraminidase-NC41 Fab complex. J Mol Biol 227 (1992) 122-148
63. Bossart-Whitaker P., Chang C.Y., Novotny J., Benjamin D.C., and Sheriff S. The crystal structure of the antibody N10-staphylococcal nuclease complex at 2.9 A resolution. J Mol Biol 253 (1995) 559-575
64. Prasad L., Sharma S., Vandonselaar M., Quail J.W., Lee J.S., Waygood E.B., Wilson K.S., Dauter Z., and Delbaere L.T. Evaluation of mutagenesis for epitode mapping. Structure of an antibody-protein antigen complex. J Biol Chem 268 (1993) 10705-10708
65. Malby R.L., Tulip W.R., Harley V.R., McKimm-Breschkin J.L., Laver W.G., Webster R.G., and Colman P.M. The structure of a complex between the NC10 antibody and influenza virus nueraminidase and comparison with the overlapping binding site of the NC41 antibody. Structure 2 (1994) 733-746
66. Lescar J., Souchon H., and Alzari P.M. Crystal structures of pheasant and guinea fowl egg-white lysozymes. Protein Sci 3 (1994) 788-798
67. Chacko S., Silverton E., Kam-Morgan L., Smith-Gill S., Cohen G., and Davies D. Structure of an antibody-lysozyme complex unexpected effect of conservative mutation. J Mol Biol 245 (1995) 261-274
68. Padlan E.A., Silverton E.W., Sheriff S., Cohen G.H., Smith-Gill S.J., and Davies D.R. Structure of an antibody-antigen complex: crystal structure of the HyHEL-10 Fab-lysozyme complex. Proc Natl Acad Sci USA 86 (1989) 5938-5942
69. Braden B.C., Souchon H., Eisele J.L., Bentley G.A., Bhat T.N., Navaza J., and Poljak R.J. Three-dimensional structures of the free and the antigen-complexed Fab from monoclonal anti-lysozyme antibody D44.1. J Mol Biol 243 (1994) 767-781
70. Chitarra V., Alzari P.M., Bentley G.A., Bhat T.N., Eisele J.L., Houdusse A., Lescar J., Souchon H., and Poljak R.J. Three-dimensional structure of a heteroclitic antigen-antibody cross-reaction complex. Proc Natl Acad Sci USA 90 (1993) 7711-7715
71. DeLano W.L. The PyMol Molecular Graphics system. DeLano Scientific, San Carlos, CA, USA (2002)