4hsa: Difference between revisions

Revision as of 10:34, 20 January 2015

Structure of interleukin 17a in complex with il17ra receptor

Structural highlights

4hsa is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	NAG, FUC, MAN
Related:	4hr9
Gene:	IL17A, CTLA8, IL17 (Homo sapiens), IL17RA, IL17R (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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

[IL17_HUMAN] Induces stromal cells to produce proinflammatory and hematopoietic cytokines. Enhances the surface expression of ICAM1/intracellular adhesion molecule 1 in fibroblasts. [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

The constituent polypeptides of the interleukin-17 family form six different homodimeric cytokines (IL-17A-F) and the heterodimeric IL-17A/F. Their interactions with IL-17 receptors A-E (IL-17RA-E) mediate host defenses while also contributing to inflammatory and autoimmune responses. IL-17A and IL-17F both preferentially engage a receptor complex containing one molecule of IL-17RA and one molecule of IL-17RC. More generally, IL-17RA appears to be a shared receptor that pairs with other members of its family to allow signaling of different IL-17 cytokines. Here we report crystal structures of homodimeric IL-17A and its complex with IL-17RA. Binding to IL-17RA at one side of the IL-17A molecule induces a conformational change in the second, symmetry-related receptor site of IL-17A. This change favors, and is sufficient to account for, the selection of a different receptor polypeptide to complete the cytokine-receptor complex. The structural results are supported by biophysical studies with IL-17A variants produced by site-directed mutagenesis.

Crystal structures of interleukin 17A and its complex with IL-17 receptor A.,Liu S, Song X, Chrunyk BA, Shanker S, Hoth LR, Marr ES, Griffor MC Nat Commun. 2013;4:1888. doi: 10.1038/ncomms2880. PMID:23695682^[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
↑ Liu S, Song X, Chrunyk BA, Shanker S, Hoth LR, Marr ES, Griffor MC. Crystal structures of interleukin 17A and its complex with IL-17 receptor A. Nat Commun. 2013;4:1888. doi: 10.1038/ncomms2880. PMID:23695682 doi:10.1038/ncomms2880

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OCA

[1] 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

[2] 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

[3] 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

[4] Liu S, Song X, Chrunyk BA, Shanker S, Hoth LR, Marr ES, Griffor MC. Crystal structures of interleukin 17A and its complex with IL-17 receptor A. Nat Commun. 2013;4:1888. doi: 10.1038/ncomms2880. PMID:23695682 doi:10.1038/ncomms2880

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[2]

[3]

[4]

@@ Line 1: / Line 1: @@
-{{STRUCTURE_4hsa|  PDB=4hsa  |  SCENE=  }}
+==Structure of interleukin 17a in complex with il17ra receptor==
-===Structure of interleukin 17a in complex with il17ra receptor===
+<StructureSection load='4hsa' size='340' side='right' caption='[[4hsa]], [[Resolution|resolution]] 3.15&Aring;' scene=''>
-{{ABSTRACT_PUBMED_23695682}}
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4hsa]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HSA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HSA FirstGlance]. <br>
-==Disease==
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hr9|4hr9]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL17A, CTLA8, IL17 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), IL17RA, IL17R ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4hsa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hsa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hsa RCSB], [http://www.ebi.ac.uk/pdbsum/4hsa PDBsum]</span></td></tr>
+</table>
+== Disease ==
 [[http://www.uniprot.org/uniprot/I17RA_HUMAN I17RA_HUMAN]] Defects in IL17RA are the cause of familial candidiasis type 5 (CANDF5) [MIM:[http://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 ==
+[[http://www.uniprot.org/uniprot/IL17_HUMAN IL17_HUMAN]] Induces stromal cells to produce proinflammatory and hematopoietic cytokines. Enhances the surface expression of ICAM1/intracellular adhesion molecule 1 in fibroblasts. [[http://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 ==
+The constituent polypeptides of the interleukin-17 family form six different homodimeric cytokines (IL-17A-F) and the heterodimeric IL-17A/F. Their interactions with IL-17 receptors A-E (IL-17RA-E) mediate host defenses while also contributing to inflammatory and autoimmune responses. IL-17A and IL-17F both preferentially engage a receptor complex containing one molecule of IL-17RA and one molecule of IL-17RC. More generally, IL-17RA appears to be a shared receptor that pairs with other members of its family to allow signaling of different IL-17 cytokines. Here we report crystal structures of homodimeric IL-17A and its complex with IL-17RA. Binding to IL-17RA at one side of the IL-17A molecule induces a conformational change in the second, symmetry-related receptor site of IL-17A. This change favors, and is sufficient to account for, the selection of a different receptor polypeptide to complete the cytokine-receptor complex. The structural results are supported by biophysical studies with IL-17A variants produced by site-directed mutagenesis.
-==Function==
+Crystal structures of interleukin 17A and its complex with IL-17 receptor A.,Liu S, Song X, Chrunyk BA, Shanker S, Hoth LR, Marr ES, Griffor MC Nat Commun. 2013;4:1888. doi: 10.1038/ncomms2880. PMID:23695682<ref>PMID:23695682</ref>
-[[http://www.uniprot.org/uniprot/IL17_HUMAN IL17_HUMAN]] Induces stromal cells to produce proinflammatory and hematopoietic cytokines. Enhances the surface expression of ICAM1/intracellular adhesion molecule 1 in fibroblasts. [[http://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>
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[4hsa]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HSA OCA].
+</div>
-==Reference==
+==See Also==
-<ref group="xtra">PMID:023695682</ref><references group="xtra"/><references/>
+*[[Interleukin|Interleukin]]
+*[[Interleukin receptor|Interleukin receptor]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Liu, S.]]
+[[Category: Liu, S]]
 [[Category: Cytokine receptor]]
 [[Category: Glycosylation]]
 [[Category: Immune system-protein binding complex]]

4hsa: Difference between revisions

Revision as of 10:34, 20 January 2015

Structure of interleukin 17a in complex with il17ra receptor

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

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