K. Yamaguchi et al., CHARACTERIZATION OF STRUCTURAL DOMAINS OF HUMAN OSTEOCLASTOGENESIS INHIBITORY FACTOR, The Journal of biological chemistry, 273(9), 1998, pp. 5117-5123
Osteoclastogenesis inhibitory factor (OCIF) is a heparin-binding secre
tary glycoprotein that belongs to the tumor necrosis factor receptor (
TNFR) family. OCIF is present both as a similar to 60-kDa monomer and
a disulfide-linked homodimer, We attempted to characterize the seven s
tructural domains of OCIF by determining the capabilities of various O
CIF mutants to inhibit osteoclastogenesis, to interact with heparin, a
nd to form dimers. We also examined a potential of domains 5 and 6, de
ath domain homologous regions (DDHs), for inducing cell death by expre
ssing OCIF/Fas fusion proteins, Our results show that: (i) the N-termi
nal portion of OCIF containing domains 1-4, which have structural simi
larity to the extracellular domains of the TNFR family proteins, is su
fficient to inhibit osteoclastogenesis; (ii) a heparin-binding site is
located in domain 7, and affinity for heparin does not correlate with
the inhibitory activity; (iii) Cys-400 in domain 7 is the residue res
ponsible for dimer formation; and (iv) the C-terminal portion containi
ng domains 5 and 6, DDHs, has a high potential for mediating a cytotox
ic signal when it is expressed in cells as an OCIF/Fas fusion protein
in which the transmembrane region of Fas is inserted in front of DDHs.