A flexible multidomain structure drives the function of the urokinase-type plasminogen activator receptor (uPAR)

Research output: Contribution to journalJournal articlepeer-review

  • Haydyn D.T. Mertens
  • Magnus Kjærgaard
  • Simon Mysling
  • Henrik Gårdsvoll
  • Thomas J. D. Jørgensen
  • Dimitri I. Svergun
  • Michael Ploug
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 languageEnglish
JournalJournal of Biological Chemistry
Volume287
Issue number41
Pages (from-to)34304-34315
Number of pages12
ISSN0021-9258
DOIs
Publication statusPublished - 2012

ID: 40513592