当前位置:科学网首页 > 小柯机器人 >详情
病毒蛋白可直接切割NLRP1来激活炎性小体
作者:小柯机器人 发布时间:2020/10/23 14:39:14

新加坡分子和细胞生物学研究所Bruno Reversade、Franklin L. Zhong等研究人员合作发现,肠病毒3C蛋白酶激活气道上皮细胞中的人类NLRP1炎性小体。 2020年10月22日,《科学》杂志在线发表了这项成果。

研究人员发现,人类NLRP1被肠病毒,例如人类鼻病毒(HRV)的3C蛋白酶(3Cpros)激活。3Cpros直接在Glu130和Gly131之间的单个位点切割人NLRP1。这种切割通过cullinZER1/ZYG11B复合物触发N-甘氨酸介导的自抑制性NLRP1 N末端片段降解,从而释放活化的C末端片段。人类HRV活病毒感染主要的人类气道上皮细胞,从而会触发NLRP1依赖性炎症小体激活和IL-18分泌。这些发现将3Cpros确立为人类NLRP1炎性小体的病原体来源触发因素,并暗示NLRP1可能与气道炎性疾病有关。
 
据了解,免疫传感蛋白对于人类先天免疫系统的功能至关重要。目前尚未完全了解人类免疫传感器同源触发的全部功能。
 
附:英文原文

Title: Enteroviral 3C protease activates the human NLRP1 inflammasome in airway epithelia

Author: Kim S. Robinson, Daniel Eng Thiam Teo, Kai Sen Tan, Gee Ann Toh, Hsiao Hui Ong, Chrissie Kaishi Lim, Kenneth Lay, Bijin Veonice Au, Tian Sheng Lew, Justin Jang Hann Chu, Vincent Tak Kwong Chow, De Yun Wang, Franklin L. Zhong, Bruno Reversade

Issue&Volume: 2020/10/22

Abstract: Immune sensor proteins are critical to the function of the human innate immune system. The full repertoire of cognate triggers for human immune sensors is not fully understood. Here, we report that human NLRP1 is activated by 3C proteases (3Cpros) of enteroviruses, such as human rhinovirus (HRV). 3Cpros directly cleave human NLRP1 at a single site between Glu130 and Gly131. This cleavage triggers N-glycine–mediated degradation of the autoinhibitory NLRP1 N-terminal fragment via the cullinZER1/ZYG11B complex, which liberates the activating C-terminal fragment. Infection of primary human airway epithelial cells by live human HRV triggers NLRP1-dependent inflammasome activation and IL-18 secretion. Our findings establish 3Cpros as a pathogen-derived trigger for the human NLRP1 inflammasome and suggest that NLRP1 may contribute to inflammatory diseases of the airway.

DOI: 10.1126/science.aay2002

Source: https://science.sciencemag.org/content/early/2020/10/21/science.aay2002

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037