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| | <StructureSection load='6ppg' size='340' side='right'caption='[[6ppg]], [[Resolution|resolution]] 2.75Å' scene=''> | | <StructureSection load='6ppg' size='340' side='right'caption='[[6ppg]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ppg]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PPG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PPG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ppg]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PPG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PPG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75Å</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=6ppg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ppg OCA], [http://pdbe.org/6ppg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ppg RCSB], [http://www.ebi.ac.uk/pdbsum/6ppg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ppg ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ppg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ppg OCA], [https://pdbe.org/6ppg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ppg RCSB], [https://www.ebi.ac.uk/pdbsum/6ppg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ppg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/IL17F_HUMAN IL17F_HUMAN]] Defects in IL17F are the cause of familial candidiasis type 6 (CANDF6) [MIM:[http://omim.org/entry/613956 613956]]. CANDF6 is a rare disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans.<ref>PMID:21350122</ref> | + | [https://www.uniprot.org/uniprot/IL17F_HUMAN IL17F_HUMAN] Defects in IL17F are the cause of familial candidiasis type 6 (CANDF6) [MIM:[https://omim.org/entry/613956 613956]. CANDF6 is a rare disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans.<ref>PMID:21350122</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IL17F_HUMAN IL17F_HUMAN]] Stimulates the production of other cytokines such as IL-6, IL-8 and granulocyte colony-stimulating factor, and can regulate cartilage matrix turnover. Stimulates PBMC and T-cell proliferation. Inhibits angiogenesis. | + | [https://www.uniprot.org/uniprot/IL17F_HUMAN IL17F_HUMAN] Stimulates the production of other cytokines such as IL-6, IL-8 and granulocyte colony-stimulating factor, and can regulate cartilage matrix turnover. Stimulates PBMC and T-cell proliferation. Inhibits angiogenesis. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6ppg" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6ppg" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[Interleukin 3D structures|Interleukin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Huang, C S]] | + | [[Category: Huang CS]] |
| - | [[Category: Hymowitz, S G]] | + | [[Category: Hymowitz SG]] |
| - | [[Category: Yin, J P]] | + | [[Category: Yin JP]] |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Il-17]]
| + | |
| Structural highlights
Disease
IL17F_HUMAN Defects in IL17F are the cause of familial candidiasis type 6 (CANDF6) [MIM:613956. CANDF6 is a rare disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans.[1]
Function
IL17F_HUMAN Stimulates the production of other cytokines such as IL-6, IL-8 and granulocyte colony-stimulating factor, and can regulate cartilage matrix turnover. Stimulates PBMC and T-cell proliferation. Inhibits angiogenesis.
Publication Abstract from PubMed
Some antibodies exhibit elevated viscosity at high concentrations, making them poorly suited for therapeutic applications requiring administration by injection such as subcutaneous or ocular delivery. Here we studied an anti-IL-13/IL-17 bispecific IgG4 antibody, which has anomalously high viscosity compared to its parent monospecific antibodies. The viscosity of the bispecific IgG4 in solution was decreased by only ~30% in the presence of NaCl, suggesting electrostatic interactions are insufficient to fully explain the drivers of viscosity. Intriguingly, addition of arginine-HCl reduced the viscosity of the bispecific IgG4 by ~50% to its parent IgG level. These data suggest that beyond electrostatics, additional types of interactions such as cation-pi and/or pi-pi may contribute to high viscosity more significantly than previously understood. Molecular dynamics simulations of antibody fragments in the mixed solution of free arginine and explicit water were conducted to identify hotspots involved in self-interactions. Exposed surface aromatic amino acids displayed an increased number of contacts with arginine. Mutagenesis of the majority of aromatic residues pinpointed by molecular dynamics simulations effectively decreased the solution's viscosity when tested experimentally. This mutational method to reduce the viscosity of a bispecific antibody was extended to a monospecific anti-GCGR IgG1 antibody with elevated viscosity. In all cases, point mutants were readily identified that both reduced viscosity and retained antigen-binding affinity. These studies demonstrate a new approach to mitigate high viscosity of some antibodies by mutagenesis of surface-exposed aromatic residues on complementarity-determining regions that may facilitate some clinical applications.
Dissecting the molecular basis of high viscosity of monospecific and bispecific IgG antibodies.,Tilegenova C, Izadi S, Yin J, Huang CS, Wu J, Ellerman D, Hymowitz SG, Walters B, Salisbury C, Carter PJ MAbs. 2020 Jan-Dec;12(1):1692764. doi: 10.1080/19420862.2019.1692764. PMID:31779513[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Puel A, Cypowyj S, Bustamante J, Wright JF, Liu L, Lim HK, Migaud M, Israel L, Chrabieh M, Audry M, Gumbleton M, Toulon A, Bodemer C, El-Baghdadi J, Whitters M, Paradis T, Brooks J, Collins M, Wolfman NM, Al-Muhsen S, Galicchio M, Abel L, Picard C, Casanova JL. Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science. 2011 Apr 1;332(6025):65-8. doi: 10.1126/science.1200439. Epub 2011 Feb, 24. PMID:21350122 doi:10.1126/science.1200439
- ↑ Tilegenova C, Izadi S, Yin J, Huang CS, Wu J, Ellerman D, Hymowitz SG, Walters B, Salisbury C, Carter PJ. Dissecting the molecular basis of high viscosity of monospecific and bispecific IgG antibodies. MAbs. 2020 Jan-Dec;12(1):1692764. doi: 10.1080/19420862.2019.1692764. PMID:31779513 doi:http://dx.doi.org/10.1080/19420862.2019.1692764
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