Organizing structural principles of the IL-17 ligand-receptor axis
DC Element | Wert | Sprache |
---|---|---|
dc.contributor.author | Wilson, Steven C. | |
dc.contributor.author | Caveney, Nathanael A. | |
dc.contributor.author | Yen, Michelle | |
dc.contributor.author | Pollmann, Christoph | |
dc.contributor.author | Xiang, Xinyu | |
dc.contributor.author | Jude, Kevin M. | |
dc.contributor.author | Hafer, Maximillian | |
dc.contributor.author | Tsutsumi, Naotaka | |
dc.contributor.author | Piehler, Jacob | |
dc.contributor.author | Garcia, K. Christopher | |
dc.date.accessioned | 2023-02-17T11:34:47Z | - |
dc.date.available | 2023-02-17T11:34:47Z | - |
dc.date.issued | 2022 | |
dc.identifier.issn | 0028-0836 | |
dc.identifier.uri | http://osnascholar.ub.uni-osnabrueck.de/handle/unios/65456 | - |
dc.description.abstract | The IL-17 family of cytokines and receptors have central roles in host defence against infection and development of inflammatory diseases(1). The compositions and structures of functional IL-17 family ligand-receptor signalling assemblies remain unclear. IL-17E (also known as IL-25) is a key regulator of type 2 immune responses and driver of inflammatory diseases, such as allergic asthma, and requires both IL-17 receptor A (IL-17RA) and IL-17RB to elicit functional responses(2). Here we studied IL-25-IL-17RB binary and IL-25-IL-17RB-IL-17RA ternary complexes using a combination of cryo-electron microscopy, single-molecule imaging and cell-based signalling approaches. The IL-25-IL-17RB-IL-17RA ternary signalling assembly is a C2-symmetric complex in which the IL-25-IL-17RB homodimer is flanked by two `wing-like' IL-17RA co-receptorsth rough a `tip-to-tip' geometry that is the key receptor-receptor interaction required for initiation of signal transduction. IL-25 interacts solely with IL-17RB to allosterically promote the formation of the IL-17RB-IL-17RA tip-to-tip interface. The resulting large separation between the receptors at the membrane-proximal level may reflect proximity constraints imposed by the intracellular domains for signalling. Cryo-electron microscopy structures of IL-17A-IL-17RA and IL-17A-IL-17RA-IL-17RC complexes reveal that thistip-to-tip architecture is a key organizing principle of the IL-17 receptor family. Furthermore, these studies reveal dual actions for IL-17RA sharing among IL-17 cytokine complexes, by either directly engaging IL-17 cytokines or alternatively functioning as a co-receptor. | |
dc.description.sponsorship | CIHR; Stanford Immunology Program training grant [5T32AI07290-33]; Stanford Immunology and Rheumatology training grant [5T32AR050942-15]; DFG [PI 405/14-1, SFB 944/P8, INST 190/146-3]; Sanofi Innovation Award; US National Institutes of Health grant [R01-AI51321]; We thank L. Montabana and C. Zhang from the Stanford University Cryo-Electron Microscopy Center (cEMc), and R. Yan and S. Yang from the Howard Hughes Medical Institute Janelia Research Campus Cryo-EM Facility for their assistance with data collection. Structural biology applications used in this project were compiled and configured by SBGrid52. We thank members of the Garcia laboratory for support and helpful discussions; R. Saxton for critical review of the manuscript; and Y. Miao and D. Siepe for advice on the SPR experiments. N.A.C. is supported by a CIHR postdoctoral fellowship. M.Y. is supported by the Stanford Immunology Program training grant (5T32AI07290-33) and the Stanford Immunology and Rheumatology training grant (5T32AR050942-15). J.P. was supported by the DFG (Imaging Facility iBiOs, PI 405/14-1 and SFB 944/P8, INST 190/146-3). K.C.G. is an investigator with the Howard Hughes Medical Institute, and is supported by a Sanofi Innovation Award and US National Institutes of Health grant R01-AI51321. | |
dc.language.iso | en | |
dc.publisher | NATURE PORTFOLIO | |
dc.relation.ispartof | NATURE | |
dc.subject | ACT1 | |
dc.subject | ADAPTER PROTEIN | |
dc.subject | AUTOIMMUNE | |
dc.subject | CELLS | |
dc.subject | CUTTING EDGE | |
dc.subject | CYTOKINE | |
dc.subject | EXPRESSION | |
dc.subject | IL-23 | |
dc.subject | INFLAMMATION | |
dc.subject | Multidisciplinary Sciences | |
dc.subject | RESPONSES | |
dc.subject | Science & Technology - Other Topics | |
dc.title | Organizing structural principles of the IL-17 ligand-receptor axis | |
dc.type | journal article | |
dc.identifier.doi | 10.1038/s41586-022-05116-y | |
dc.identifier.isi | ISI:000844487500001 | |
dc.description.volume | 609 | |
dc.description.issue | 7927 | |
dc.description.startpage | 622+ | |
dc.contributor.orcid | 0000-0003-4828-3479 | |
dc.contributor.orcid | 0000-0002-8358-2960 | |
dc.contributor.orcid | 0000-0002-7382-3388 | |
dc.contributor.orcid | 0000-0002-3675-5136 | |
dc.contributor.orcid | 0000-0002-3617-7145 | |
dc.identifier.eissn | 1476-4687 | |
dc.publisher.place | HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY | |
dcterms.isPartOf.abbreviation | Nature | |
dcterms.oaStatus | Green Published, hybrid | |
local.import.remains | affiliations : Stanford University; Stanford University; University Osnabruck; Howard Hughes Medical Institute; Stanford University | |
local.import.remains | earlyaccessdate : JUL 2022 | |
local.import.remains | web-of-science-index : Science Citation Index Expanded (SCI-EXPANDED) | |
crisitem.author.dept | FB 05 - Biologie/Chemie | - |
crisitem.author.deptid | fb05 | - |
crisitem.author.orcid | 0000-0002-2143-2270 | - |
crisitem.author.parentorg | Universität Osnabrück | - |
crisitem.author.netid | PiJa938 | - |
Seitenaufrufe
2
Letzte Woche
0
0
Letzter Monat
0
0
geprüft am 18.05.2024