Crystal structures of interleukin 17A and its complex with IL-17 receptor A

Shenping Liu (), Xi Song, Boris A. Chrunyk, Suman Shanker, Lise R. Hoth, Eric S. Marr and Matthew C. Griffor
Additional contact information
Shenping Liu: Structural Biology and Biophysics Group, Pfizer Groton Laboratories
Xi Song: Structural Biology and Biophysics Group, Pfizer Groton Laboratories
Boris A. Chrunyk: Structural Biology and Biophysics Group, Pfizer Groton Laboratories
Suman Shanker: Structural Biology and Biophysics Group, Pfizer Groton Laboratories
Lise R. Hoth: Structural Biology and Biophysics Group, Pfizer Groton Laboratories
Eric S. Marr: Structural Biology and Biophysics Group, Pfizer Groton Laboratories
Matthew C. Griffor: Structural Biology and Biophysics Group, Pfizer Groton Laboratories

Nature Communications, 2013, vol. 4, issue 1, 1-9

Abstract: Abstract 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.

Date: 2013
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms2880 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2880

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms2880

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().