5bnq
Crystal structure of hRANKL-mRANK complex
Structural highlights
DiseaseTNF11_HUMAN Autosomal recessive malignant osteopetrosis. The disease is caused by mutations affecting the gene represented in this entry. FunctionTNF11_HUMAN Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.[1] Publication Abstract from PubMedAnti-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. A RANKL mutant used as an inter-species vaccine for efficient immunotherapy of osteoporosis.,Liu C, Zhao Y, He W, Wang W, Chen Y, Zhang S, Ma Y, Gohda J, Ishida T, Walter TS, Owens RJ, Stuart DI, Ren J, Gao B Sci Rep. 2015 Sep 28;5:14150. doi: 10.1038/srep14150. PMID:26412210[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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