基础医学与临床2025，Vol.45Issue(9)：1151-1157,7.DOI:10.16352/j.issn.1001-6325.2025.09.1151
ACE2蛋白Cys141、Cys344和Cys498位点的棕榈酰化修饰促进其在细胞外囊泡的定位
Palmitoylation of ACE2 at Cys141,Cys344,and Cys498 facilitates its extracellular vesicles localization
摘要
Abstract
Objective To identify S-palmitoylation sites on angiotensin-converting enzyme 2(ACE2),the cellular receptor for severe acute respiratory syndrome corona virus(SARS-CoV)and SARS-CoV-2,and to investigate the functional relevance of these modifications in regulating ACE2 localization and activity.Methods An optimized multi-site mutagenesis strategy was performed by simultaneously substitution of all eight cysteine(Cys)residuesin ACE2 by serine to create a non-palmitoylatable mutant(8CS).Then individual cysteine residues were re-introduced one by one.Palmitoylation level of mutants was evaluated using a bioorthogonal click chemistry method to identify palmitoylation-competent residues.Immune-fluorescence staining and extra-cellular vesicle isolation assays were then used to evaluate the impact of specific palmitoylation sites on ACE2 sub-cellular localization.Results An efficient strategy for multi-site palmitoylation site mapping was optimized and successfully identified three critical palmitoylation sites on ACE2:Cys141,Cys344 and Cys498.Functional analyses showed that palmi-toylation of these sites significantly promotes the enrichment of ACE2 in extra-cellular vesicles.Conclusions S-palmitoylation at Cys141,Cys344 and Cys498 is essential for the trafficking of ACE2 to extra-cellular vesicles,which suggests a potential regulatory mechanism of its impact on viral receptor presentation and ACE2-associated signaling pathways.关键词
S-棕榈酰化/多点突变/翻译后修饰/细胞外囊泡/血管紧张素转化酶2(ACE2)Key words
S-palmitoylation/multi-site mutagenesis/post-translational modification/extra cellular vesicle/angiotensin-converting enzyme 2(ACE2)分类
医药卫生引用本文复制引用
阳晶晶,马艳,王悦,孙阳,李盼,郭峰..ACE2蛋白Cys141、Cys344和Cys498位点的棕榈酰化修饰促进其在细胞外囊泡的定位[J].基础医学与临床,2025,45(9):1151-1157,7.基金项目
国家自然科学基金(82370051,82373905) （82370051,82373905）
江苏省研究生科研与实践创新计划项目(KYCX23_2944) （KYCX23_2944）
基础医学国家级实验教学示范中心学生科创项目(2024BMS29) （2024BMS29）
