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TitleA flexible multidomain structure drives the function of the urokinase-type plasminogen activator receptor (uPAR).
Journal, issue, pagesJ Biol Chem, Vol. 287, Issue 41, Page 34304-34315, Year 2012
Publish dateOct 5, 2012
AuthorsHaydyn D T Mertens / Magnus Kjaergaard / Simon Mysling / Henrik Gårdsvoll / Thomas J D Jørgensen / Dmitri I Svergun / Michael Ploug /
PubMed AbstractThe 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 linksJ Biol Chem / PubMed:22896701 / PubMed Central
MethodsSAS (X-ray synchrotron)
Structure data

SASDAT4:
uPAR wild-type (Urokinase plasminogen activator surface receptor, uPAR)
Method: SAXS/SANS

SASDAU4:
uPAR H47C/N259C (Urokinase plasminogen activator surface receptor, uPAR)
Method: SAXS/SANS

SASDAV4: uPAR wild-type AE105 complex (Urokinase plasminogen activator surface receptor, uPAR + synthetic peptide AE105, AE105)
Method: SAXS/SANS

SASDAW4: uPAR wild-type AE234 complex (Urokinase plasminogen activator surface receptor, uPAR + synthetic peptide AE234, AE234)
Method: SAXS/SANS

SASDAX4: uPAR wild-type ATF complex (Urokinase plasminogen activator surface receptor, uPAR + Urokinase-type plasminogen activator, ATF)
Method: SAXS/SANS

Source
  • Homo sapiens (human)

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