Dimerization interface of osteoprotegerin revealed by hydrogen-deuterium exchange mass spectrometry.

ABSTRACT: Previous structural studies of osteoprotegerin (OPG), a crucial negative regulator of bone remodeling and osteoclastogenesis, were mostly limited to the N-terminal ligand-binding domains. It is now known that the three C-terminal domains of OPG also play essential roles in its function by mediating OPG dimerization, OPG-heparan sulfate (HS) interactions, and formation of the OPG-HS-receptor activator of nuclear factor κB ligand (RANKL) ternary complex. Employing hydrogen-deuterium exchange MS methods, here we investigated the structure of full-length OPG in complex with HS or RANKL in solution. Our data revealed two noteworthy aspects of the OPG structure. First, we found that the interconnection between the N- and C-terminal domains is much more rigid than previously thought, possibly bec

SUBMITTER: Xiao Y 

PROVIDER: S-EPMC6231129 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature