A flexible multidomain structure drives the function of the urokinase-type plasminogen activator receptor (uPAR).
J Biol Chem
; 287(41): 34304-15, 2012 Oct 05.
Article
en En
| MEDLINE
| ID: mdl-22896701
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 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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Vitronectina
/
Matriz Extracelular
/
Receptores del Activador de Plasminógeno Tipo Uroquinasa
/
Proteolisis
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2012
Tipo del documento:
Article
País de afiliación:
Dinamarca