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Denosumab mimics the natural decoy receptor osteoprotegerin by interacting with its major binding site on RANKL

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Denosumab mimics the natural decoy receptor osteoprotegerin by interacting with its major binding site on RANKL. / Schieferdecker, Aneta; Voigt, Mareike; Riecken, Kristoffer; Braig, Friederike; Schinke, Thorsten; Loges, Sonja; Bokemeyer, Carsten; Fehse, Boris; Binder, Mascha.

In: ONCOTARGET, Vol. 5, No. 16, 30.08.2014, p. 6647-53.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schieferdecker, A, Voigt, M, Riecken, K, Braig, F, Schinke, T, Loges, S, Bokemeyer, C, Fehse, B & Binder, M 2014, 'Denosumab mimics the natural decoy receptor osteoprotegerin by interacting with its major binding site on RANKL', ONCOTARGET, vol. 5, no. 16, pp. 6647-53.

APA

Schieferdecker, A., Voigt, M., Riecken, K., Braig, F., Schinke, T., Loges, S., Bokemeyer, C., Fehse, B., & Binder, M. (2014). Denosumab mimics the natural decoy receptor osteoprotegerin by interacting with its major binding site on RANKL. ONCOTARGET, 5(16), 6647-53.

Vancouver

Schieferdecker A, Voigt M, Riecken K, Braig F, Schinke T, Loges S et al. Denosumab mimics the natural decoy receptor osteoprotegerin by interacting with its major binding site on RANKL. ONCOTARGET. 2014 Aug 30;5(16):6647-53.

Bibtex

@article{e1420f8ad047457fb3f8174ccdc5a986,
title = "Denosumab mimics the natural decoy receptor osteoprotegerin by interacting with its major binding site on RANKL",
abstract = "Bone homeostasis critically relies on the RANKL-RANK-OPG axis which can be targeted by the fully human monoclonal antibody denosumab in conditions with increased bone resporption such as bone metastases. The binding site and therefore the molecular mechanism by which this antibody inhibits RANKL has not been characterized so far. Here, we used random peptide phage display library screenings to identify the denosumab epitope on RANKL. Alignments of phage derived peptide sequences with RANKL suggested that this antibody recognized a linear epitope between position T233 and Y241. Mutational analysis confirmed the core residues as critical for this interaction. The spatial localization of this epitope on a 3-dimensional model of RANKL showed that it overlapped with the major binding sites of OPG and RANK on RANKL. We conclude that denosumab inhibits RANKL by both functional and molecular mimicry of the natural decoy receptor OPG.",
author = "Aneta Schieferdecker and Mareike Voigt and Kristoffer Riecken and Friederike Braig and Thorsten Schinke and Sonja Loges and Carsten Bokemeyer and Boris Fehse and Mascha Binder",
year = "2014",
month = aug,
day = "30",
language = "English",
volume = "5",
pages = "6647--53",
journal = "ONCOTARGET",
issn = "1949-2553",
publisher = "IMPACT JOURNALS LLC",
number = "16",

}

RIS

TY - JOUR

T1 - Denosumab mimics the natural decoy receptor osteoprotegerin by interacting with its major binding site on RANKL

AU - Schieferdecker, Aneta

AU - Voigt, Mareike

AU - Riecken, Kristoffer

AU - Braig, Friederike

AU - Schinke, Thorsten

AU - Loges, Sonja

AU - Bokemeyer, Carsten

AU - Fehse, Boris

AU - Binder, Mascha

PY - 2014/8/30

Y1 - 2014/8/30

N2 - Bone homeostasis critically relies on the RANKL-RANK-OPG axis which can be targeted by the fully human monoclonal antibody denosumab in conditions with increased bone resporption such as bone metastases. The binding site and therefore the molecular mechanism by which this antibody inhibits RANKL has not been characterized so far. Here, we used random peptide phage display library screenings to identify the denosumab epitope on RANKL. Alignments of phage derived peptide sequences with RANKL suggested that this antibody recognized a linear epitope between position T233 and Y241. Mutational analysis confirmed the core residues as critical for this interaction. The spatial localization of this epitope on a 3-dimensional model of RANKL showed that it overlapped with the major binding sites of OPG and RANK on RANKL. We conclude that denosumab inhibits RANKL by both functional and molecular mimicry of the natural decoy receptor OPG.

AB - Bone homeostasis critically relies on the RANKL-RANK-OPG axis which can be targeted by the fully human monoclonal antibody denosumab in conditions with increased bone resporption such as bone metastases. The binding site and therefore the molecular mechanism by which this antibody inhibits RANKL has not been characterized so far. Here, we used random peptide phage display library screenings to identify the denosumab epitope on RANKL. Alignments of phage derived peptide sequences with RANKL suggested that this antibody recognized a linear epitope between position T233 and Y241. Mutational analysis confirmed the core residues as critical for this interaction. The spatial localization of this epitope on a 3-dimensional model of RANKL showed that it overlapped with the major binding sites of OPG and RANK on RANKL. We conclude that denosumab inhibits RANKL by both functional and molecular mimicry of the natural decoy receptor OPG.

M3 - SCORING: Journal article

C2 - 25138051

VL - 5

SP - 6647

EP - 6653

JO - ONCOTARGET

JF - ONCOTARGET

SN - 1949-2553

IS - 16

ER -