5BNQ

Crystal structure of hRANKL-mRANK complex

Summary for 5BNQ

• Entry DOI: 10.2210/pdb5bnq/pdb
• Descriptor: Tumor necrosis factor ligand superfamily member 11, Tumor necrosis factor receptor superfamily member 11A, PHOSPHATE ION, ... (6 entities in total)
• Functional Keywords: rank, rankl, rankl-rank complex, tnfsf11, tnfrsf11a, tnf superfamily, cytokine
• Biological source: Homo sapiens (Human); More
• Cellular location: Isoform 1: Cell membrane; Single-pass type II membrane protein. Isoform 3: Cell membrane; Single-pass type II membrane protein. Isoform 2: Cytoplasm . Tumor necrosis factor ligand superfamily member 11, soluble form: Secreted : O14788; Cell membrane ; Single-pass type I membrane protein : O35305
• Total number of polymer chains: 2
• Total formula weight: 42758.80

Authors

Ren, J. (deposition date: 2015-05-26, release date: 2015-10-14, Last modification date: 2024-11-20)

Primary citation

Liu, C.,Zhao, Y.,He, W.,Wang, W.,Chen, Y.,Zhang, S.,Ma, Y.,Gohda, J.,Ishida, T.,Walter, T.S.,Owens, R.J.,Stuart, D.I.,Ren, J.,Gao, B.
A RANKL mutant used as an inter-species vaccine for efficient immunotherapy of osteoporosis.
Sci Rep, 5:14150-14150, 2015

PubMed Abstract: Anti-cytokine therapeutic antibodies have been demonstrated to be effective in the treatment of several auto-immune disorders. However, The problems in antibody manufacture and the immunogenicity caused by multiple doses of antibodies inspire people to use auto-cytokine as immunogen to induce anti-cytokine antibodies. Nevertheless, the tolerance for inducing immune response against self-antigen has hindered the wide application of the strategy. To overcome the tolerance, here we proposed a strategy using the inter-species cytokine as immunogen for active immunization (TISCAI) to induce anti-cytokine antibody. As a proof of concept, an inter-species cytokine RANKL was successfully used as immunogen to induce anti-RANKL immune response. Furthermore, to prevent undesirable side-effects, the human RANKL was mutated based on the crystal structure of the complex of human RANKL and its rodent counterpart receptor RANK. We found, the antibodies produced blocked the osteoclast development in vitro and osteoporosis in OVX rat models. The results demonstrated this strategy adopted is very useful for general anti-cytokine immunotherapy for different diseases settings.

PubMed: 26412210
DOI: 10.1038/srep14150

Experimental method

X-RAY DIFFRACTION (2.8 Å)