5VI4

IL-33/ST2/IL-1RAcP ternary complex structure

Summary for 5VI4

• Entry DOI: 10.2210/pdb5vi4/pdb
• Descriptor: Interleukin-33, Interleukin-1 receptor-like 1, Interleukin-1 receptor accessory protein, ... (4 entities in total)
• Functional Keywords: cytokine, cytokine receptor, signaling, signaling protein
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 6
• Total formula weight: 185661.45

Authors

Guenther, S.,Sundberg, E.J. (deposition date: 2017-04-13, release date: 2017-09-27, Last modification date: 2024-10-16)

Primary citation

Gunther, S.,Deredge, D.,Bowers, A.L.,Luchini, A.,Bonsor, D.A.,Beadenkopf, R.,Liotta, L.,Wintrode, P.L.,Sundberg, E.J.
IL-1 Family Cytokines Use Distinct Molecular Mechanisms to Signal through Their Shared Co-receptor.
Immunity, 47:510-523.e4, 2017

PubMed Abstract: Within the interleukin 1 (IL-1) cytokine family, IL-1 receptor accessory protein (IL-1RAcP) is the co-receptor for eight receptor-cytokine pairs, including those involving cytokines IL-1β and IL-33. Unlike IL-1β, IL-33 does not have a signaling complex that includes both its cognate receptor, ST2, and the shared co-receptor IL-1RAcP, which we now present here. Although the IL-1β and IL-33 complexes shared structural features and engaged identical molecular surfaces of IL-1RAcP, these cytokines had starkly different strategies for co-receptor engagement and signal activation. Our data suggest that IL-1β binds to IL-1RI to properly present the cytokine to IL-1RAcP, whereas IL-33 binds to ST2 in order to conformationally constrain the cognate receptor in an IL-1RAcP-receptive state. These findings indicate that members of the IL-1 family of cytokines use distinct molecular mechanisms to signal through their shared co-receptor, and they provide the foundation from which to design new therapies to target IL-33 signaling.

PubMed: 28930661
DOI: 10.1016/j.immuni.2017.08.004

Experimental method

X-RAY DIFFRACTION (2.792 Å)