5n9b

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of unliganded human IL-17RA

Structural highlights

5n9b is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.9Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

I17RA_HUMAN Defects in IL17RA are the cause of familial candidiasis type 5 (CANDF5) [MIM:613953. CANDF5 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

I17RA_HUMAN Receptor for IL17A, IL17F and, in dimer with IL17RE, for IL17C. Binds its IL17A ligand with low affinity, suggesting that additional components are involved in IL17A-induced signaling.^[2] ^[3]

Publication Abstract from PubMed

Signaling through innate immune receptors such as the Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) superfamily proceeds via the assembly of large membrane-proximal complexes or "signalosomes." Although structurally distinct, the IL-17 receptor family triggers cellular responses that are typical of innate immune receptors. The IL-17RA receptor subunit is shared by several members of the IL-17 family. Using a combination of crystallographic, biophysical, and mutational studies, we show that IL-17A, IL-17F, and IL-17A/F induce IL-17RA dimerization. X-ray analysis of the heteromeric IL-17A complex with the extracellular domains of the IL-17RA and IL-17RC receptors reveals that cytokine-induced IL-17RA dimerization leads to the formation of a 2:2:2 hexameric signaling assembly. Furthermore, we demonstrate that the formation of the IL-17 signalosome potentiates IL-17-induced IL-36gamma and CXCL1 mRNA expression in human keratinocytes, compared with a dimerization-defective IL-17RA variant.

IL-17-induced dimerization of IL-17RA drives the formation of the IL-17 signalosome to potentiate signaling.,Goepfert A, Barske C, Lehmann S, Wirth E, Willemsen J, Gudjonsson JE, Ward NL, Sarkar MK, Hemmig R, Kolbinger F, Rondeau JM Cell Rep. 2022 Oct 18;41(3):111489. doi: 10.1016/j.celrep.2022.111489. PMID:36260993^[4]

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

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
↑ Ramirez-Carrozzi V, Sambandam A, Luis E, Lin Z, Jeet S, Lesch J, Hackney J, Kim J, Zhou M, Lai J, Modrusan Z, Sai T, Lee W, Xu M, Caplazi P, Diehl L, de Voss J, Balazs M, Gonzalez L Jr, Singh H, Ouyang W, Pappu R. IL-17C regulates the innate immune function of epithelial cells in an autocrine manner. Nat Immunol. 2011 Oct 12;12(12):1159-66. doi: 10.1038/ni.2156. PMID:21993848 doi:10.1038/ni.2156
↑ Ely LK, Fischer S, Garcia KC. Structural basis of receptor sharing by interleukin 17 cytokines. Nat Immunol. 2009 Dec;10(12):1245-51. Epub 2009 Oct 18. PMID:19838198 doi:10.1038/ni.1813
↑ Goepfert A, Barske C, Lehmann S, Wirth E, Willemsen J, Gudjonsson JE, Ward NL, Sarkar MK, Hemmig R, Kolbinger F, Rondeau JM. IL-17-induced dimerization of IL-17RA drives the formation of the IL-17 signalosome to potentiate signaling. Cell Rep. 2022 Oct 18;41(3):111489. doi: 10.1016/j.celrep.2022.111489. PMID:36260993 doi:http://dx.doi.org/10.1016/j.celrep.2022.111489

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5n9b"

Categories: Homo sapiens | Large Structures | Goepfert A | Rondeau J-M

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5n9b is ON HOLD  until Paper Publication
+==Crystal Structure of unliganded human IL-17RA==
+<StructureSection load='5n9b' size='340' side='right'caption='[[5n9b]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5n9b]] is a 1 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=5N9B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N9B FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=5n9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n9b OCA], [https://pdbe.org/5n9b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n9b RCSB], [https://www.ebi.ac.uk/pdbsum/5n9b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n9b ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/I17RA_HUMAN I17RA_HUMAN] Defects in IL17RA are the cause of familial candidiasis type 5 (CANDF5) [MIM:[https://omim.org/entry/613953 613953]. CANDF5 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 ==
+[https://www.uniprot.org/uniprot/I17RA_HUMAN I17RA_HUMAN] Receptor for IL17A, IL17F and, in dimer with IL17RE, for IL17C. Binds its IL17A ligand with low affinity, suggesting that additional components are involved in IL17A-induced signaling.<ref>PMID:21993848</ref> <ref>PMID:19838198</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Signaling through innate immune receptors such as the Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) superfamily proceeds via the assembly of large membrane-proximal complexes or "signalosomes." Although structurally distinct, the IL-17 receptor family triggers cellular responses that are typical of innate immune receptors. The IL-17RA receptor subunit is shared by several members of the IL-17 family. Using a combination of crystallographic, biophysical, and mutational studies, we show that IL-17A, IL-17F, and IL-17A/F induce IL-17RA dimerization. X-ray analysis of the heteromeric IL-17A complex with the extracellular domains of the IL-17RA and IL-17RC receptors reveals that cytokine-induced IL-17RA dimerization leads to the formation of a 2:2:2 hexameric signaling assembly. Furthermore, we demonstrate that the formation of the IL-17 signalosome potentiates IL-17-induced IL-36gamma and CXCL1 mRNA expression in human keratinocytes, compared with a dimerization-defective IL-17RA variant.
-Authors: RONDEAU, J.-M., GOEPFERT, A.
+IL-17-induced dimerization of IL-17RA drives the formation of the IL-17 signalosome to potentiate signaling.,Goepfert A, Barske C, Lehmann S, Wirth E, Willemsen J, Gudjonsson JE, Ward NL, Sarkar MK, Hemmig R, Kolbinger F, Rondeau JM Cell Rep. 2022 Oct 18;41(3):111489. doi: 10.1016/j.celrep.2022.111489. PMID:36260993<ref>PMID:36260993</ref>
-Description: Crystal Structure of unliganded human IL-17RA
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Rondeau, J.-M]]
+<div class="pdbe-citations 5n9b" style="background-color:#fffaf0;"></div>
-[[Category: Goepfert, A]]
+==See Also==
+*[[Interleukin receptor 3D structures|Interleukin receptor 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Goepfert A]]
+[[Category: Rondeau J-M]]

5n9b

From Proteopedia

Current revision

Crystal Structure of unliganded human IL-17RA

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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