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PMID: 16393951 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

Evidence for ligand-independent multimerization of the IL-17 receptor.

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 176 ·No. 2 ·2006-01-15 ·Pages 711-5

Kramer JM, Yi L, Shen F, Maitra A, Jiao X, Jin T, Gaffen SL

Abstract

IL-17 and its receptor are founding members of a novel inflammatory cytokine family. To date, only one IL-17 receptor subunit has been identified, termed IL-17RA. All known cytokine receptors consist of a complex of multiple subunits. Although IL-17-family cytokines exist as homodimers, the configuration and stoichiometry of the IL-17R complex remain unknown. We used fluorescence resonance energy transfer (FRET) to determine whether IL-17RA subunits multimerize, and, if so, whether they are preassembled in the plasma membrane. HEK293 cells coexpressing IL-17RA fused to cyan or yellow fluorescent proteins (CFP or YFP) were used to evaluate FRET before and after IL-17A or IL-17F treatment. In the absence of ligand, IL-17RA molecules exhibited significant specific FRET efficiency, demonstrating that they exist in a multimeric, preformed receptor complex. Strikingly, treatment with IL-17A or IL-17F markedly reduced FRET efficiency, suggesting that IL-17RA subunits within the IL-17R complex undergo a conformational change upon ligand binding.

MeSH Terms
Animals Bacterial Proteins/chemistry,genetics,metabolism Cell Line Fluorescence Resonance Energy Transfer Green Fluorescent Proteins/chemistry,genetics,metabolism Humans In Vitro Techniques Interleukin-17/metabolism Ligands Luminescent Proteins/chemistry,genetics,metabolism Mice Models, Molecular Multiprotein Complexes Protein Structure, Quaternary Protein Subunits Receptors, Interleukin/chemistry,genetics,metabolism Recombinant Fusion Proteins/chemistry,genetics,metabolism Transfection
Chemicals
Bacterial Proteins Cyan Fluorescent Protein Interleukin-17 Ligands Luminescent Proteins Multiprotein Complexes Protein Subunits Receptors, Interleukin Recombinant Fusion Proteins yellow fluorescent protein, Bacteria Green Fluorescent Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Kramer Jill M
Department of Oral Biology, School of Dental Medicine, University at Buffalo, State University of New York, Buffalo, NY 14214, USA.
Yi Ling
Shen Fang
Maitra Amarnath
Jiao Xuanmao
Jin Tian
Gaffen Sarah L
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Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
0022-1767
DOI
10.4049/jimmunol.176.2.711
Published
2006-01-15
Pages
711-5
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC2973994
Subset
IM
Grants
NIAMS NIH HHS · AR050458 · United States
Intramural NIH HHS · United States
NIAMS NIH HHS · R21 AR050458 · United States
NIDCR NIH HHS · F30 DE014831-04 · United States
NIDCR NIH HHS · DE014831 · United States
NIDCR NIH HHS · F30 DE014831 · United States
Corrections
ErratumIn
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External Links
PubMed source DOI: 10.4049/jimmunol.176.2.711 PMC Full Text View journal details
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