8URV

Solution NMR structure of pro-IL-18

This is a non-PDB format compatible entry.

Summary for 8URV

• Entry DOI: 10.2210/pdb8urv/pdb
• NMR Information: BMRB: 31122
• Descriptor: Interleukin-18 (1 entity in total)
• Functional Keywords: interleukin-18, beta-trefoil, immune system
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 22350.22

Authors

Bonin, J.P.,Aramini, J.M.,Kay, L.E. (deposition date: 2023-10-26, release date: 2024-05-29, Last modification date: 2024-07-24)

Primary citation

Dong, Y.,Bonin, J.P.,Devant, P.,Liang, Z.,Sever, A.I.M.,Mintseris, J.,Aramini, J.M.,Du, G.,Gygi, S.P.,Kagan, J.C.,Kay, L.E.,Wu, H.
Structural transitions enable interleukin-18 maturation and signaling.
Immunity, 57:1533-, 2024

PubMed Abstract: Several interleukin-1 (IL-1) family members, including IL-1β and IL-18, require processing by inflammasome-associated caspases to unleash their activities. Here, we unveil, by cryoelectron microscopy (cryo-EM), two major conformations of the complex between caspase-1 and pro-IL-18. One conformation is similar to the complex of caspase-4 and pro-IL-18, with interactions at both the active site and an exosite (closed conformation), and the other only contains interactions at the active site (open conformation). Thus, pro-IL-18 recruitment and processing by caspase-1 is less dependent on the exosite than the active site, unlike caspase-4. Structure determination by nuclear magnetic resonance uncovers a compact fold of apo pro-IL-18, which is similar to caspase-1-bound pro-IL-18 but distinct from cleaved IL-18. Binding sites for IL-18 receptor and IL-18 binding protein are only formed upon conformational changes after pro-IL-18 cleavage. These studies show how pro-IL-18 is selected as a caspase-1 substrate, and why cleavage is necessary for its inflammatory activity.

PubMed: 38733997
DOI: 10.1016/j.immuni.2024.04.015

Experimental method

SOLUTION NMR