Biochemical characterization of a disease-causing human osteoprotegerin variant.

ABSTRACT: Recently, a human mutation of OPG was identified to be associated with familial forms of osteoarthritis. This missense mutation (c.1205A =  > T; p.Stop402Leu) occurs on the stop codon of OPG, which results in a 19-residue appendage to the C-terminus (OPG⁺¹⁹). The biochemical consequence of this unusual sequence alteration remains unknown. Here we expressed OPG⁺¹⁹ in 293 cells and the mutant OPG was purified to homogeneity by heparin affinity chromatography and size exclusion chromatography. We found that in sharp contrast to wildtype OPG, which mainly exists in dimeric form, OPG⁺¹⁹ had a strong tendency to form higher-order oligomers. To our surprise, the hyper-oligomerization of OPG⁺¹⁹ had no impact on how it binds cell surface heparan sulfate,

SUBMITTER: Luo Y 

PROVIDER: S-EPMC9464236 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature