The C-type mannose receptor and its homolog
Endo180 (or uPARAP, for urokinase plasminogen
activator receptor-associated protein) mediate the
endocytic uptake of collagen by macrophages and fi-
broblasts. This process is required for normal tissue
remodeling, but also facilitates the growth and
dissemination of tumors. We have determined the
crystal structure at 2.5 A˚ resolution of the N-terminal
region of Endo180, consisting of a ricin-like domain,
a fibronectin type II (FN2) domain, and two C-type
lectin (CTL) domains. The L-shaped arrangement of
these domains creates a shallow trench spanning
the FN2 and CTL1 domains, which was shown by
mutagenesis to bind triple-helical and denatured
collagen. Small-angle X-ray scattering showed that
the L-shaped structure is maintained in solution at
neutral and acidic pH, irrespective of calcium ion
loading. Collagen binding was equally unaffected
by acidic pH, suggesting that collagen release in endosomes
is not regulated by changes within the
Endo180 N-terminal region.