Structure-function of the TNF receptor-like cysteine-rich domain of osteoprotegerin

Joon Shin, Young Mee Kim, Song Zhe Li, Sung Kil Lim, Weontae Lee

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Osteoprotegerin (OPG) is a soluble decoy receptor that inhibits osteoclastogenesis and is closely associated with bone resorption processes. We have designed and determined the solution structures of potent OPG analogue peptides, derived from sequences of the cysteine-rich domain of OPG. The inhibitory effects of the peptides on osteoclastogenesis are dose-dependent (10-6M-10-4M), and the activity of the linear peptide at 10-4M is ten-fold higher than that of the cyclic OPG peptide. Both linear and cyclic peptides have a β-turn-like conformation and the cyclic peptide has a rigid conformation, suggesting that structural flexibility is an important factor for receptor binding. Based on structural and biochemical information about RANKL and the OPG peptides, we suggest that complex formation between the peptide and RANKL is mediated by both hydrophobic and hydrogen bonding interactions. These results provide structural insights that should aid in the design of peptidyl-mimetic inhibitors for treating metabolic bone diseases caused by abnormal osteoclast recruitmen.

Original languageEnglish
Pages (from-to)352-357
Number of pages6
JournalMolecules and Cells
Volume25
Issue number3
Publication statusPublished - 2008 May 31

Fingerprint

Osteoprotegerin
Tumor Necrosis Factor Receptors
Cysteine
Cyclic Peptides
Peptides
Osteogenesis
Metabolic Bone Diseases
Osteoclasts
Hydrogen Bonding
Bone Resorption

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Shin, Joon ; Kim, Young Mee ; Li, Song Zhe ; Lim, Sung Kil ; Lee, Weontae. / Structure-function of the TNF receptor-like cysteine-rich domain of osteoprotegerin. In: Molecules and Cells. 2008 ; Vol. 25, No. 3. pp. 352-357.
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Structure-function of the TNF receptor-like cysteine-rich domain of osteoprotegerin. / Shin, Joon; Kim, Young Mee; Li, Song Zhe; Lim, Sung Kil; Lee, Weontae.

In: Molecules and Cells, Vol. 25, No. 3, 31.05.2008, p. 352-357.

Research output: Contribution to journalArticle

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