New insights into the role of Methionine 199 in the function of Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) and bone homeostasis

Research output: ThesisMaster's Thesis

257 Downloads (Pure)

Abstract

Receptor activator of NF-kB ligand (RANKL) is a critical cytokine for osteoclast differentiation, while its mutants have not been well characterized. A natural mutation in human RANKL at residue M199 was described in patients with osteoclast­ poor autosomal recessive osteopetrosis. We generated three RANKLmutants using site directed mutagenesis and studied their efficacy on osteoclastic activity. We found that RANKLmutants exhibit a drastically reduced ability to induce osteoclast formation, osteoclastic polarization, bone resorption as well as downstream signaling due to misfolded RANKL. Our results show that M199 is a structurally-sensitive residue representative of a curative motif for next-generation anti-resorptive drugs.
Original languageEnglish
QualificationMasters
Awarding Institution
  • The University of Western Australia
Supervisors/Advisors
  • Xu, Jiake, Supervisor
  • Pavlos, Nathan, Supervisor
  • Tickner, Jennifer, Supervisor
Award date14 May 2018
DOIs
Publication statusUnpublished - 2018

Fingerprint Dive into the research topics of 'New insights into the role of Methionine 199 in the function of Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) and bone homeostasis'. Together they form a unique fingerprint.

Cite this