4HSA

Structure of interleukin 17a in complex with il17ra receptor

Summary for 4HSA

• Entry DOI: 10.2210/pdb4hsa/pdb
• Related: 4HR9
• Descriptor: Interleukin-17A, Interleukin-17 receptor A, alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: cytokine receptor, glycosylation, immune system-protein binding complex, immune system/protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 129144.73

Authors

Liu, S. (deposition date: 2012-10-29, release date: 2013-05-22, Last modification date: 2020-07-29)

Primary citation

Liu, S.,Song, X.,Chrunyk, B.A.,Shanker, S.,Hoth, L.R.,Marr, E.S.,Griffor, M.C.
Crystal structures of interleukin 17A and its complex with IL-17 receptor A.
Nat Commun, 4:1888-1888, 2013

PubMed 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.

PubMed: 23695682
DOI: 10.1038/ncomms2880

Experimental method

X-RAY DIFFRACTION (3.15 Å)