5BNQ: Crystal Structure Of Hrankl-mrank Complex

Citation:
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.
PDB ID: 5BNQDownload
MMDB ID: 133333
PDB Deposition Date: 2015/5/26
Updated in MMDB: 2015/11
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Mus musculus
Similar Structures:
Biological Unit for 5BNQ: hexameric; determined by author and by software (PISA)
Molecular Components in 5BNQ
Label Count Molecule
Proteins (6 molecules)
3
Tumor Necrosis Factor Ligand Superfamily Member 11(Gene symbol: TNFSF11)
Molecule annotation
3
Tumor Necrosis Factor Receptor Superfamily Member 11A(Gene symbol: Tnfrsf11a)
Molecule annotation
Chemicals (29 molecules)
1
10
2
16
3
3
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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