美国哈佛大学吴皓等研究人员合作发现，结构转变使白细胞介素-18成熟并发出信号。相关论文于2024年5月10日在线发表在《免疫》杂志上。

研究人员表示，包括IL-1β和IL-18在内的几种IL-1家族成员需要经过炎性体相关caspase的加工才能释放其活性。

附：英文原文

Title: Structural transitions enable interleukin-18 maturation and signaling

Author: Ying Dong, Jeffrey P. Bonin, Pascal Devant, Zhuoyi Liang, Alexander I.M. Sever, Julian Mintseris, James M. Aramini, Gang Du, Stephen P. Gygi, Jonathan C. Kagan, Lewis E. Kay, Hao Wu

Issue&Volume: 2024-05-10

Abstract: Several interleukin-1 (IL-1) family members, including IL-1β and IL-18, require processingby inflammasome-associated caspases to unleash their activities. Here, we unveil,by cryoelectron microscopy (cryo-EM), two major conformations of the complex betweencaspase-1 and pro-IL-18. One conformation is similar to the complex of caspase-4 andpro-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 exositethan the active site, unlike caspase-4. Structure determination by nuclear magneticresonance uncovers a compact fold of apo pro-IL-18, which is similar to caspase-1-boundpro-IL-18 but distinct from cleaved IL-18. Binding sites for IL-18 receptor and IL-18binding 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 cleavageis necessary for its inflammatory activity.

DOI: 10.1016/j.immuni.2024.04.015

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00220-6