A flexible multidomain structure drives the function of the urokinase-type plasminogen activator receptor (uPAR)
Research output: Contribution to journal › Journal article › peer-review
The urokinase-type plasminogen activator receptor (uPAR) provides a rendezvous between proteolytic degradation of the extracellular matrix and integrin mediated adhesion to vitronectin. These processes are however tightly linked as the high-affinity binding of urokinase regulates the binding of uPAR to matrix-embedded vitronectin. Although crystal structures exist to define the corresponding static bi- and trimolecular receptor complexes it is evident that the dynamic property of uPAR plays a decisive role for its function. In the present study, we combine small angle X-ray scattering, hydrogen-deuterium exchange, and surface plasmon resonance to develop a structural model describing the allosteric regulation of uPAR. We show that the flexibility of its N-terminal domain provides the key for understanding this allosteric mechanism. Importantly, our model has direct implications for understanding uPAR-assisted cell adhesion and migration as well as for translational research including targeted intervention therapy and non-invasive tumor imaging in vivo.
Original language | English |
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Journal | Journal of Biological Chemistry |
Volume | 287 |
Issue number | 41 |
Pages (from-to) | 34304-34315 |
Number of pages | 12 |
ISSN | 0021-9258 |
DOIs | |
Publication status | Published - 2012 |
ID: 40513592