| Literature DB >> 23695682 |
Shenping Liu1, Xi Song, Boris A Chrunyk, Suman Shanker, Lise R Hoth, Eric S Marr, Matthew C Griffor.
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.Entities:
Mesh：
Substances：
Year: 2013 PMID： 23695682 DOI： 10.1038/ncomms2880
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919