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.
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Acknowledgements
This research is supported by grants from the US National Institutes of Health (HL08658) and the American Heart Association (0330089N) (to M.H.) and from the British Heart Foundation (to A.Z.). Data for this study were measured at beam lines ID19 and ID24 of Advanced Photon Sources and at beam line X29 of the the National Synchrotron Light Source.
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Q.H. and L.L. performed the experiments and solved the structures; M.H. refined the structures and wrote the paper; A.Z., A.P.M., G.C.P., J.C., D.E.S., B.F. and B.C.F. provided reagents and/or ideas to this work.
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Supplementary Figure 1, Supplementary Tables 1 and 2, and Supplementary Methods (PDF 1265 kb)
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Huai, Q., Zhou, A., Lin, L. et al. Crystal structures of two human vitronectin, urokinase and urokinase receptor complexes. Nat Struct Mol Biol 15, 422–423 (2008). https://doi.org/10.1038/nsmb.1404
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DOI: https://doi.org/10.1038/nsmb.1404
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