浙江大学曹戟、李君、何俏军课题组在研究中取得进展。他们研究发现zDHHC20驱动的CD80 S-棕榈酰化是其共刺激功能所必需的。该项研究成果发表在2024年3月11日出版的《中国药理学报》上。

在这项研究中，小组研究了CD80的翻译后修饰及其生物学意义。通过代谢标记策略，课题组研究人员发现CD80在跨膜和细胞质区域的多个半胱氨酸残基(Cys261/262/266/271)上被S-棕榈酰化。课题组人员进一步确定zDHHC20是一个真正的棕榈酰转移酶，决定CD80的S-棕榈酰化水平。

该研究组证明了S-棕榈酰化保护CD80蛋白免受泛素化降解，调节蛋白的稳定性，并确保其准确的质膜定位。棕榈酰化缺陷突变体(4CS) CD80破坏了这些功能，最终导致其在T细胞活化时的共刺激功能丧失。综上所述，他们的结果描述了CD80通过S-棕榈酰化的新的后转录修饰作为调节T细胞激活时CD80的机制。

据了解，CD80是一种跨膜糖蛋白，属于B7家族，已成为通过CD28或CTLA4轴调节T细胞的关键分子。CD80参与的免疫平衡调节是一个精细调节的过程，阐明CD80功能调节的潜在机制具有重要意义。

附：英文原文

Title: zDHHC20-driven S-palmitoylation of CD80 is required for its costimulatory function

Author: Lu, Bin, Sun, Yi-yun, Chen, Bo-ya, Yang, Bo, He, Qiao-jun, Li, Jun, Cao, Ji

Issue&Volume: 2024-03-11

Abstract: CD80 is a transmembrane glycoprotein belonging to the B7 family, which has emerged as a crucial molecule in T cell modulation via the CD28 or CTLA4 axes. CD80-involved regulation of immune balance is a finely tuned process and it is important to elucidate the underlying mechanism for regulating CD80 function. In this study we investigated the post-translational modification of CD80 and its biological relevance. By using a metabolic labeling strategy, we found that CD80 was S-palmitoylated on multiple cysteine residues (Cys261/262/266/271) in both the transmembrane and the cytoplasmic regions. We further identified zDHHC20 as a bona fide palmitoyl-transferase determining the S-palmitoylation level of CD80. We demonstrated that S-palmitoylation protected CD80 protein from ubiquitination degradation, regulating the protein stability, and ensured its accurate plasma membrane localization. The palmitoylation-deficient mutant (4CS) CD80 disrupted these functions, ultimately resulting in the loss of its costimulatory function upon T cell activation. Taken together, our results describe a new post-translational modification of CD80 by S-palmitoylation as a novel mechanism for the regulation of CD80 upon T cell activation.

DOI: 10.1038/s41401-024-01248-1

Source: https://www.nature.com/articles/s41401-024-01248-1