5bnq

From Proteopedia

(Difference between revisions)

Revision as of 03:50, 16 October 2015

Crystal structure of hRANKL-mRANK complex

Structural highlights

5bnq is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Disease

[TNF11_HUMAN] Autosomal recessive malignant osteopetrosis. The disease is caused by mutations affecting the gene represented in this entry.

Function

[TNF11_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] [TNR11_MOUSE] Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis. Involved in the regulation of interactions between T-cells and dendritic cells.^[2] ^[3]

Publication Abstract from PubMed

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.

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Luan X, Lu Q, Jiang Y, Zhang S, Wang Q, Yuan H, Zhao W, Wang J, Wang X. Crystal Structure of Human RANKL Complexed with Its Decoy Receptor Osteoprotegerin. J Immunol. 2012 Jul 1;189(1):245-52. Epub 2012 Jun 4. PMID:22664871 doi:10.4049/jimmunol.1103387
↑ Nakagawa N, Kinosaki M, Yamaguchi K, Shima N, Yasuda H, Yano K, Morinaga T, Higashio K. RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis. Biochem Biophys Res Commun. 1998 Dec 18;253(2):395-400. PMID:9878548 doi:S0006-291X(98)99788-1
↑ Liu C, Walter TS, Huang P, Zhang S, Zhu X, Wu Y, Wedderburn LR, Tang P, Owens RJ, Stuart DI, Ren J, Gao B. Structural and functional insights of RANKL-RANK interaction and signaling. J Immunol. 2010 Jun 15;184(12):6910-9. Epub 2010 May 14. PMID:20483727 doi:10.4049/jimmunol.0904033
↑ 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. A RANKL mutant used as an inter-species vaccine for efficient immunotherapy of osteoporosis. Sci Rep. 2015 Sep 28;5:14150. doi: 10.1038/srep14150. PMID:26412210 doi:http://dx.doi.org/10.1038/srep14150

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5bnq"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==Crystal structure of hRANKL-mRANK complex==
+<StructureSection load='5bnq' size='340' side='right' caption='[[5bnq]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5bnq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BNQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BNQ FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5bnq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bnq OCA], [http://pdbe.org/5bnq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bnq RCSB], [http://www.ebi.ac.uk/pdbsum/5bnq PDBsum]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/TNF11_HUMAN TNF11_HUMAN]] Autosomal recessive malignant osteopetrosis. The disease is caused by mutations affecting the gene represented in this entry.
+== Function ==
+[[http://www.uniprot.org/uniprot/TNF11_HUMAN TNF11_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.<ref>PMID:22664871</ref>  [[http://www.uniprot.org/uniprot/TNR11_MOUSE TNR11_MOUSE]] Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis. Involved in the regulation of interactions between T-cells and dendritic cells.<ref>PMID:9878548</ref> <ref>PMID:20483727</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+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.
-The entry 5bnq is ON HOLD  until Paper Publication
+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<ref>PMID:26412210</ref>
-Authors: Ren, J.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: Crystal structure of hRANKL-mRANK complex
+<div class="pdbe-citations 5bnq" style="background-color:#fffaf0;"></div>
-[[Category: Unreleased Structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Ren, J]]
+[[Category: Cytokine]]
+[[Category: Rank]]
+[[Category: Rankl]]
+[[Category: Rankl-rank complex]]
+[[Category: Tnf superfamily]]
+[[Category: Tnfrsf11a]]
+[[Category: Tnfsf11]]

5bnq

From Proteopedia

Revision as of 03:50, 16 October 2015

Crystal structure of hRANKL-mRANK complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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