+Search query
-Structure paper
Title | A flexible multidomain structure drives the function of the urokinase-type plasminogen activator receptor (uPAR). |
---|---|
Journal, issue, pages | J Biol Chem, Vol. 287, Issue 41, Page 34304-34315, Year 2012 |
Publish date | Oct 5, 2012 |
Authors | Haydyn D T Mertens / Magnus Kjaergaard / Simon Mysling / Henrik Gårdsvoll / Thomas J D Jørgensen / Dmitri I Svergun / Michael Ploug / |
PubMed Abstract | The urokinase-type plasminogen activator receptor (uPAR) provides a rendezvous between proteolytic degradation of the extracellular matrix and integrin-mediated adhesion to vitronectin. These ...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 because 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 in 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. |
External links | J Biol Chem / PubMed:22896701 / PubMed Central |
Methods | SAS (X-ray synchrotron) |
Structure data | SASDAT4: SASDAU4: SASDAV4: uPAR wild-type AE105 complex (Urokinase plasminogen activator surface receptor, uPAR + synthetic peptide AE105, AE105) SASDAW4: uPAR wild-type AE234 complex (Urokinase plasminogen activator surface receptor, uPAR + synthetic peptide AE234, AE234) SASDAX4: uPAR wild-type ATF complex (Urokinase plasminogen activator surface receptor, uPAR + Urokinase-type plasminogen activator, ATF) |
Source |
|