4NUX

Structure of receptor A

Summary for 4NUX

• Entry DOI: 10.2210/pdb4nux/pdb
• Descriptor: Interleukin-17 receptor A (2 entities in total)
• Functional Keywords: sefir domain, immune system, cytokine, receptor, autoimmune inflammatory
• Biological source: Homo sapiens (human)
• Cellular location: Isoform 1: Membrane; Single-pass type I membrane protein (By similarity). Isoform 2: Secreted: Q96F46
• Total number of polymer chains: 1
• Total formula weight: 24771.56

Authors

Zhang, B.,Han, Y.,Deng, J. (deposition date: 2013-12-04, release date: 2014-05-14, Last modification date: 2024-02-28)

Primary citation

Zhang, B.,Liu, C.,Qian, W.,Han, Y.,Li, X.,Deng, J.
Structure of the unique SEFIR domain from human interleukin 17 receptor A reveals a composite ligand-binding site containing a conserved alpha-helix for Act1 binding and IL-17 signaling.
Acta Crystallogr.,Sect.D, 70:1476-1483, 2014

PubMed Abstract: Interleukin 17 (IL-17) cytokines play a crucial role in mediating inflammatory and autoimmune diseases. A unique intracellular signaling domain termed SEFIR is found within all IL-17 receptors (IL-17Rs) as well as the key adaptor protein Act1. SEFIR-mediated protein-protein interaction is a crucial step in IL-17 cytokine signaling. Here, the 2.3 Å resolution crystal structure of the SEFIR domain of IL-17RA, the most commonly shared receptor for IL-17 cytokine signaling, is reported. The structure includes the complete SEFIR domain and an additional α-helical C-terminal extension, which pack tightly together to form a compact unit. Structural comparison between the SEFIR domains of IL-17RA and IL-17RB reveals substantial differences in protein topology and folding. The uniquely long insertion between strand βC and helix αC in IL-17RA SEFIR is mostly well ordered, displaying a helix (αCC'ins) and a flexible loop (CC'). The DD' loop in the IL-17RA SEFIR structure is much shorter; it rotates nearly 90° with respect to the counterpart in the IL-17RB SEFIR structure and shifts about 12 Å to accommodate the αCC'ins helix without forming any knots. Helix αC was identified as critical for its interaction with Act1 and IL-17-stimulated gene expression. The data suggest that the heterotypic SEFIR-SEFIR association via helix αC is a conserved and signature mechanism specific for IL-17 signaling. The structure also suggests that the downstream motif of IL-17RA SEFIR together with helix αC could provide a composite ligand-binding surface for recruiting Act1 during IL-17 signaling.

PubMed: 24816115
DOI: 10.1107/S1399004714005227

Experimental method

X-RAY DIFFRACTION (2.295 Å)