加拿大圣迈克尔学院 Gregory D. Fairn、加拿大玛格丽特公主癌症中心 Brian Raught、浙江大学医学院孙启明和Dante Neculai课题组合作发现，细菌感知需要核苷酸结合寡聚化结构域（NOD）样受体1和2（NOD1/2）的棕榈酰化修饰。该项研究成果发表在10月25日出版的《科学》杂志上。

研究人员发现，膜募集和免疫信号传导需要NOD1/2 S-棕榈酰化。棕榈酰转移酶ZDHHC5是催化此翻译后修饰的关键酶，并且研究人员还发现几种与疾病相关的NOD2突变与其S-棕榈酰化缺陷有关。因此，ZDHHC5介导的NOD1/2的S-棕榈酰化对于其对肽聚糖的应答以及进行有效免疫应答至关重要。

据介绍，NOD1/2是细胞内模式识别蛋白，可响应与微生物相关的肽聚糖而激活免疫信号通路。NOD1/2信号传导需要招募到包含细菌的内体和其他细胞内膜，而破坏NOD1/2膜定位与炎症性肠病和其他炎症性疾病有关。但是，对于这一招募过程知之甚少。

附：英文原文

Title: Palmitoylation of NOD1 and NOD2 is required for bacterial sensing

Author: Yan Lu, Yuping Zheng, étienne Coyaud, Chao Zhang, Apiraam Selvabaskaran, Yuyun Yu, Zizhen Xu, Xialian Weng, Ji Shun Chen, Ying Meng, Neil Warner, Xiawei Cheng, Yangyang Liu, Bingpeng Yao, Hu Hu, Zonping Xia, Aleixo M. Muise, Amira Klip, John H. Brumell, Stephen E. Girardin, Songmin Ying, Gregory D. Fairn, Brian Raught, Qiming Sun, Dante Neculai

Issue&Volume: 2019/10/25

Abstract: The nucleotide oligomerization domain (NOD)–like receptors 1 and 2 (NOD1/2) are intracellular pattern-recognition proteins that activate immune signaling pathways in response to peptidoglycans associated with microorganisms. Recruitment to bacteria-containing endosomes and other intracellular membranes is required for NOD1/2 signaling, and NOD1/2 mutations that disrupt membrane localization are associated with inflammatory bowel disease and other inflammatory conditions. However, little is known about this recruitment process. We found that NOD1/2 S-palmitoylation is required for membrane recruitment and immune signaling. ZDHHC5 was identified as the palmitoyltransferase responsible for this critical posttranslational modification, and several disease-associated mutations in NOD2 were found to be associated with defective S-palmitoylation. Thus, ZDHHC5-mediated S-palmitoylation of NOD1/2 is critical for their ability to respond to peptidoglycans and to mount an effective immune response.

DOI: 10.1126/science.aau6391

Source: https://science.sciencemag.org/content/366/6464/460