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Structural basis of interaction between urokinase-type plasminogen activator and its receptor.

Barinka C, Parry G, Callahan J, Shaw DE, Kuo A, Bdeir K, Cines DB, Mazar A, Lubkowski J
J Mol Biol 363 482-95 (2006)
Cited: 73 times
EuropePMC logo PMID: 16979660

Abstract

Recent studies indicate that binding of the urokinase-type plasminogen activator (uPA) to its high-affinity receptor (uPAR) orchestrates uPAR interactions with other cellular components that play a pivotal role in diverse (patho-)physiological processes, including wound healing, angiogenesis, inflammation, and cancer metastasis. However, notwithstanding the wealth of biochemical data available describing the activities of uPAR, little is known about the exact mode of uPAR/uPA interactions or the presumed conformational changes that accompany uPA/uPAR engagement. Here, we report the crystal structure of soluble urokinase plasminogen activator receptor (suPAR), which contains the three domains of the wild-type receptor but lacks the cell-surface anchoring sequence, in complex with the amino-terminal fragment of urokinase-type plasminogen activator (ATF), at the resolution of 2.8 A. We report the 1.9 A crystal structure of free ATF. Our results provide a structural basis, represented by conformational changes induced in uPAR, for several published biochemical observations describing the nature of uPAR/uPA interactions and provide insight into mechanisms that may be responsible for the cellular responses induced by uPA binding.

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  1. Structural Biology and Protein Engineering of Thrombolytics. Mican J, Toul M, Bednar D, Damborsky J. Comput Struct Biotechnol J 17 917-938 (2019)
  2. Can EGCG Alleviate Symptoms of Down Syndrome by Altering Proteolytic Activity? Wyganowska-Świątkowska M, Matthews-Kozanecka M, Matthews-Brzozowska T, Skrzypczak-Jankun E, Jankun J. Int J Mol Sci 19 E248 (2018)

Articles - 2i9b mentioned but not cited (13)

  1. Protein-protein docking benchmark version 4.0. Hwang H, Vreven T, Janin J, Weng Z. Proteins 78 3111-3114 (2010)
  2. MEGADOCK: an all-to-all protein-protein interaction prediction system using tertiary structure data. Ohue M, Matsuzaki Y, Uchikoga N, Ishida T, Akiyama Y. Protein Pept Lett 21 766-778 (2014)
  3. Mimicry of the regulatory role of urokinase in lamellipodia formation by introduction of a non-native interdomain disulfide bond in its receptor. Gårdsvoll H, Kjaergaard M, Jacobsen B, Kriegbaum MC, Huang M, Ploug M. J Biol Chem 286 43515-43526 (2011)
  4. Single amino acid substitutions in the chemotactic sequence of urokinase receptor modulate cell migration and invasion. Bifulco K, Longanesi-Cattani I, Franco P, Pavone V, Mugione P, Di Carluccio G, Masucci MT, Arra C, Pirozzi G, Stoppelli MP, Carriero MV. PLoS One 7 e44806 (2012)
  5. Protein-protein binding site identification by enumerating the configurations. Guo F, Li SC, Wang L, Zhu D. BMC Bioinformatics 13 158 (2012)
  6. Prediction of Protein-Protein Interaction Sites Using Convolutional Neural Network and Improved Data Sets. Xie Z, Deng X, Shu K. Int J Mol Sci 21 E467 (2020)
  7. Attention mechanism enhanced LSTM with residual architecture and its application for protein-protein interaction residue pairs prediction. Liu J, Gong X. BMC Bioinformatics 20 609 (2019)
  8. Cryo-EM Data Are Superior to Contact and Interface Information in Integrative Modeling. de Vries SJ, Chauvot de Beauchêne I, Schindler CE, Zacharias M. Biophys J 110 785-797 (2016)
  9. Focused grid-based resampling for protein docking and mapping. Mamonov AB, Moghadasi M, Mirzaei H, Zarbafian S, Grove LE, Bohnuud T, Vakili P, Ch Paschalidis I, Vajda S, Kozakov D. J Comput Chem 37 961-970 (2016)
  10. In silico docking of urokinase plasminogen activator and integrins. Degryse B, Fernandez-Recio J, Citro V, Blasi F, Cubellis MV. BMC Bioinformatics 9 Suppl 2 S8 (2008)
  11. Predictions of novel Schistosoma mansoni - human protein interactions consistent with experimental data. White Bear J, Long T, Skinner D, McKerrow JH. Sci Rep 8 13092 (2018)
  12. Fold combinations in multi-domain proteins. Naveenkumar N, Kumar G, Sowdhamini R, Srinivasan N, Vishwanath S. Bioinformation 15 342-350 (2019)
  13. Potential role of kringle-integrin interaction in plasmin and uPA actions (a hypothesis). Takada Y. J Biomed Biotechnol 2012 136302 (2012)


Reviews citing this publication (14)

  1. New insights into the molecular mechanisms of the fibrinolytic system. Rijken DC, Lijnen HR. J Thromb Haemost 7 4-13 (2009)
  2. The urokinase receptor: focused cell surface proteolysis, cell adhesion and signaling. Blasi F, Sidenius N. FEBS Lett 584 1923-1930 (2010)
  3. Three-finger snake neurotoxins and Ly6 proteins targeting nicotinic acetylcholine receptors: pharmacological tools and endogenous modulators. Tsetlin VI. Trends Pharmacol Sci 36 109-123 (2015)
  4. Contribution of platelets, the coagulation and fibrinolytic systems to cutaneous wound healing. Opneja A, Kapoor S, Stavrou EX. Thromb Res 179 56-63 (2019)
  5. Transforming growth factor-β, matrix metalloproteinases, and urokinase-type plasminogen activator interaction in the cancer epithelial to mesenchymal transition. Santibanez JF, Obradović H, Kukolj T, Krstić J. Dev Dyn 247 382-395 (2018)
  6. Structure-driven design of radionuclide tracers for non-invasive imaging of uPAR and targeted radiotherapy. The tale of a synthetic peptide antagonist. Ploug M. Theranostics 3 467-476 (2013)
  7. The Urokinase Receptor (uPAR) as a "Trojan Horse" in Targeted Cancer Therapy: Challenges and Opportunities. Metrangolo V, Ploug M, Engelholm LH. Cancers (Basel) 13 5376 (2021)
  8. Molecular imaging of the urokinase plasminogen activator receptor: opportunities beyond cancer. Baart VM, Houvast RD, de Geus-Oei LF, Quax PHA, Kuppen PJK, Vahrmeijer AL, Sier CFM. EJNMMI Res 10 87 (2020)
  9. Therapeutic Strategies Targeting Urokinase and Its Receptor in Cancer. Masucci MT, Minopoli M, Di Carluccio G, Motti ML, Carriero MV. Cancers (Basel) 14 498 (2022)
  10. Targeting the Urokinase-Type Plasminogen Activator Receptor (uPAR) in Human Diseases With a View to Non-invasive Imaging and Therapeutic Intervention. Leth JM, Ploug M. Front Cell Dev Biol 9 732015 (2021)
  11. Vascular targeting of antithrombotic agents. Carnemolla R, Muzykantov VR. IUBMB Life 63 632-639 (2011)
  12. Utility of P-SEP, sTREM-1 and suPAR as Novel Sepsis Biomarkers in SARS-CoV-2 Infection. Dholariya S, Parchwani DN, Singh R, Radadiya M, Katoch CDS. Indian J Clin Biochem 37 131-138 (2022)
  13. Can components of the plasminogen activation system predict the outcome of kidney transplants? Jankun J, Khan OA, Mostafa HI, Sindhwani P, Skrzypczak-Jankun E. Cent Eur J Immunol 43 222-230 (2018)
  14. suPAR to Risk-Stratify Patients With Malaria. Stefanova V, Crowley VM, Weckman AM, Kain KC. Front Immunol 13 931321 (2022)

Articles citing this publication (44)

  1. uPAR-induced cell adhesion and migration: vitronectin provides the key. Madsen CD, Ferraris GM, Andolfo A, Cunningham O, Sidenius N. J Cell Biol 177 927-939 (2007)
  2. 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. Gårdsvoll H, Ploug M. J Biol Chem 282 13561-13572 (2007)
  3. Structure-based engineering of species selectivity in the interaction between urokinase and its receptor: implication for preclinical cancer therapy. Lin L, Gårdsvoll H, Huai Q, Huang M, Ploug M. J Biol Chem 285 10982-10992 (2010)
  4. Structural basis for EGFR ligand sequestration by Argos. Klein DE, Stayrook SE, Shi F, Narayan K, Lemmon MA. Nature 453 1271-1275 (2008)
  5. A flexible multidomain structure drives the function of the urokinase-type plasminogen activator receptor (uPAR). Mertens HD, Kjaergaard M, Mysling S, Gårdsvoll H, Jørgensen TJ, Svergun DI, Ploug M. J Biol Chem 287 34304-34315 (2012)
  6. The soluble form of urokinase receptor promotes angiogenesis through its Ser⁸⁸-Arg-Ser-Arg-Tyr⁹² chemotactic sequence. Bifulco K, Longanesi-Cattani I, Gala M, DI Carluccio G, Masucci MT, Pavone V, Lista L, Arra C, Stoppelli MP, Carriero MV. J Thromb Haemost 8 2789-2799 (2010)
  7. An urokinase receptor antagonist that inhibits cell migration by blocking the formyl peptide receptor. Bifulco K, Longanesi-Cattani I, Gargiulo L, Maglio O, Cataldi M, De Rosa M, Stoppelli MP, Pavone V, Carriero MV. FEBS Lett 582 1141-1146 (2008)
  8. Number and brightness image analysis reveals ATF-induced dimerization kinetics of uPAR in the cell membrane. Hellriegel C, Caiolfa VR, Corti V, Sidenius N, Zamai M. FASEB J 25 2883-2897 (2011)
  9. Urokinase type plasminogen activator receptor (uPAR) as a new therapeutic target in cancer. Montuori N, Pesapane A, Rossi FW, Giudice V, De Paulis A, Selleri C, Ragno P. Transl Med UniSa 15 15-21 (2016)
  10. Transforming growth factor-Beta and urokinase-type plasminogen activator: dangerous partners in tumorigenesis-implications in skin cancer. Santibanez JF. ISRN Dermatol 2013 597927 (2013)
  11. 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 (αM). Xu X, Cai Y, Wei Y, Donate F, Juarez J, Parry G, Chen L, Meehan EJ, Ahn RW, Ugolkov A, Dubrovskyi O, O'Halloran TV, Huang M, Mazar AP. PLoS One 9 e85349 (2014)
  12. Serum-stable RNA aptamers to urokinase-type plasminogen activator blocking receptor binding. Dupont DM, Madsen JB, Hartmann RK, Tavitian B, Ducongé F, Kjems J, Andreasen PA. RNA 16 2360-2369 (2010)
  13. A Machine Learning Approach for Hot-Spot Detection at Protein-Protein Interfaces. Melo R, Fieldhouse R, Melo A, Correia JD, Cordeiro MN, Gümüş ZH, Costa J, Bonvin AM, Moreira IS. Int J Mol Sci 17 E1215 (2016)
  14. Cleavage of the urokinase receptor (uPAR) on oral cancer cells: regulation by transforming growth factor - β1 (TGF-β1) and potential effects on migration and invasion. Magnussen SN, Hadler-Olsen E, Costea DE, Berg E, Jacobsen CC, Mortensen B, Salo T, Martinez-Zubiaurre I, Winberg JO, Uhlin-Hansen L, Svineng G. BMC Cancer 17 350 (2017)
  15. Cyclization of the urokinase receptor-derived ser-arg-ser-arg-tyr Peptide generates a potent inhibitor of trans-endothelial migration of monocytes. Yousif AM, Minopoli M, Bifulco K, Ingangi V, Di Carluccio G, Merlino F, Motti ML, Grieco P, Carriero MV. PLoS One 10 e0126172 (2015)
  16. The inhibitory effect of HKa in endothelial cell tube formation is mediated by disrupting the uPA-uPAR complex and inhibiting its signaling and internalization. Liu Y, Cao DJ, Sainz IM, Guo YL, Colman RW. Am J Physiol Cell Physiol 295 C257-67 (2008)
  17. Urokinase plasminogen activator receptor in adipose tissue macrophages of morbidly obese subjects. Cancello R, Rouault C, Guilhem G, Bedel JF, Poitou C, Di Blasio AM, Basdevant A, Tordjman J, Clément K. Obes Facts 4 17-25 (2011)
  18. The urokinase receptor-derived cyclic peptide [SRSRY] suppresses neovascularization and intravasation of osteosarcoma and chondrosarcoma cells. Ingangi V, Bifulco K, Yousif AM, Ragone C, Motti ML, Rea D, Minopoli M, Botti G, Scognamiglio G, Fazioli F, Gallo M, De Chiara A, Arra C, Grieco P, Carriero MV. Oncotarget 7 54474-54487 (2016)
  19. Zinc phthalocyanine conjugated with the amino-terminal fragment of urokinase for tumor-targeting photodynamic therapy. Chen Z, Xu P, Chen J, Chen H, Hu P, Chen X, Lin L, Huang Y, Zheng K, Zhou S, Li R, Chen S, Liu J, Xue J, Huang M. Acta Biomater 10 4257-4268 (2014)
  20. Retro-inverso Urokinase Receptor Antagonists for the Treatment of Metastatic Sarcomas. Carriero MV, Bifulco K, Ingangi V, Costantini S, Botti G, Ragone C, Minopoli M, Motti ML, Rea D, Scognamiglio G, Botti G, Arra C, Ciliberto G, Pessi A. Sci Rep 7 1312 (2017)
  21. Targeting the cross-talk between Urokinase receptor and Formyl peptide receptor type 1 to prevent invasion and trans-endothelial migration of melanoma cells. Ragone C, Minopoli M, Ingangi V, Botti G, Fratangelo F, Pessi A, Stoppelli MP, Ascierto PA, Ciliberto G, Motti ML, Carriero MV. J Exp Clin Cancer Res 36 180 (2017)
  22. Urokinase receptor promotes ovarian cancer cell dissemination through its 84-95 sequence. Bifulco K, Votta G, Ingangi V, Di Carluccio G, Rea D, Losito S, Montuori N, Ragno P, Stoppelli MP, Arra C, Carriero MV. Oncotarget 5 4154-4169 (2014)
  23. Protein-binding RNA aptamers affect molecular interactions distantly from their binding sites. Dupont DM, Thuesen CK, Bøtkjær KA, Behrens MA, Dam K, Sørensen HP, Pedersen JS, Ploug M, Jensen JK, Andreasen PA. PLoS One 10 e0119207 (2015)
  24. A doxycycline-inducible urokinase receptor (uPAR) upregulates uPAR activities including resistance to anoikis in human prostate cancer cell lines. Hasanuzzaman M, Kutner R, Agha-Mohammadi S, Reiser J, Sehgal I. Mol Cancer 6 34 (2007)
  25. Domain 2 of uPAR regulates single-chain urokinase-mediated angiogenesis through β1-integrin and VEGFR2. Larusch GA, Merkulova A, Mahdi F, Shariat-Madar Z, Sitrin RG, Cines DB, Schmaier AH. Am J Physiol Heart Circ Physiol 305 H305-20 (2013)
  26. Selective suicide gene therapy of colon cancer exploiting the urokinase plasminogen activator receptor promoter. Teimoori-Toolabi L, Azadmanesh K, Amanzadeh A, Zeinali S. BioDrugs 24 131-146 (2010)
  27. Involvement of the soluble urokinase receptor in chondrosarcoma cell mobilization. Bifulco K, Longanesi-Cattani I, Masucci MT, De Chiara A, Fazioli F, Di Carluccio G, Pirozzi G, Gallo M, La Rocca A, Apice G, Rocco G, Carriero MV. Sarcoma 2011 842842 (2011)
  28. Did evolution create a flexible ligand-binding cavity in the urokinase receptor through deletion of a plesiotypic disulfide bond? Leth JM, Mertens HDT, Leth-Espensen KZ, Jørgensen TJD, Ploug M. J Biol Chem 294 7403-7418 (2019)
  29. D2A sequence of the urokinase receptor induces cell growth through αvβ3 integrin and EGFR. Eden G, Archinti M, Arnaudova R, Andreotti G, Motta A, Furlan F, Citro V, Cubellis MV, Degryse B. Cell Mol Life Sci 75 1889-1907 (2018)
  30. Structure-function relationship of an Urokinase Receptor-derived peptide which inhibits the Formyl Peptide Receptor type 1 activity. Minopoli M, Polo A, Ragone C, Ingangi V, Ciliberto G, Pessi A, Sarno S, Budillon A, Costantini S, Carriero MV. Sci Rep 9 12169 (2019)
  31. Mapping the putative binding site for uPA protein in Esophageal Cancer-Related Gene 2 by heteronuclear NMR method. Geng Y, Feng Y, Xie T, Dai Y, Wang J, Lu SH. Arch Biochem Biophys 479 153-157 (2008)
  32. Urokinase-type plasminogen activator-like proteases in teleosts lack genuine receptor-binding epidermal growth factor-like domains. Bager R, Kristensen TK, Jensen JK, Szczur A, Christensen A, Andersen LM, Johansen JS, Larsen N, Baatrup E, Huang M, Ploug M, Andreasen PA. J Biol Chem 287 27526-27536 (2012)
  33. Plasma tissue-type plasminogen activator increases fibrinolytic activity of exogenous urokinase-type plasminogen activator. Shenkman B, Livnat T, Budnik I, Tamarin I, Einav Y, Martinowitz U. Blood Coagul Fibrinolysis 23 729-733 (2012)
  34. A cleavage-resistant urokinase plasminogen activator receptor exhibits dysregulated cell-surface clearance. Nieves EC, Manchanda N. J Biol Chem 285 12595-12603 (2010)
  35. Interaction between kringle and growth-factor-like domains in the urokinase molecule: possible role in stimulation of chemotaxis. Stepanova VV, Beloglazova IB, Gursky YG, Bibilashvily RS, Parfyonova YV, Tkachuk VA. Biochemistry (Mosc) 73 252-260 (2008)
  36. Ab initio molecular orbital calculations on specific interactions between urokinase-type plasminogen activator and its receptor. Nagase K, Kobayashi H, Yoshikawa E, Kurita N. J Mol Graph Model 28 46-53 (2009)
  37. Computational Approaches and Analysis for a Spatio-Structural-Temporal Invasive Carcinoma Model. Hodgkinson A, Chaplain MAJ, Domschke P, Trucu D. Bull Math Biol 80 701-737 (2018)
  38. Crystal structure and cellular functions of uPAR dimer. Yu S, Sui Y, Wang J, Li Y, Li H, Cao Y, Chen L, Jiang L, Yuan C, Huang M. Nat Commun 13 1665 (2022)
  39. Mapping the topographic epitope landscape on the urokinase plasminogen activator receptor (uPAR) by surface plasmon resonance and X-ray crystallography. Zhao B, Gandhi S, Yuan C, Luo Z, Li R, Gårdsvoll H, de Lorenzi V, Sidenius N, Huang M, Ploug M. Data Brief 5 107-113 (2015)
  40. The effects of amino-acid mutations on specific interactions between urokinase-type plasminogen activator and its receptor: Ab initio molecular orbital calculations. Tsuji S, Kasumi T, Nagase K, Yoshikawa E, Kobayashi H, Kurita N. J Mol Graph Model 29 975-984 (2011)
  41. Structural investigations of recombinant urokinase growth factor-like domain. Beloglazova IB, Beabealashvilli RSh, Gursky YG, Bocharov EV, Mineev KS, Parfenova EV, Tkachuk VA. Biochemistry (Mosc) 78 517-530 (2013)
  42. Multifaced Roles of the Urokinase System in the Regulation of Stem Cell Niches. Dergilev KV, Stepanova VV, Beloglazova IB, Tsokolayev ZI, Parfenova EV. Acta Naturae 10 19-32 (2018)
  43. The Association of PLAUR Genotype and Soluble suPAR Serum Level with COVID-19-Related Lung Damage Severity. Nekrasova LA, Shmakova AA, Samokhodskaya LM, Kirillova KI, Stoyanova SS, Mershina EA, Nazarova GB, Rubina KA, Semina EV, Kamalov AA. Int J Mol Sci 23 16210 (2022)
  44. Ab initio molecular simulations for proposing novel peptide inhibitors blocking the ligand-binding pocket of urokinase receptor. Mizushima T, Sugimoto T, Kasumi T, Araki K, Kobayashi H, Kurita N. J Mol Model 20 2292 (2014)


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