Palmitoylation of ACE2 at Cys141,Cys344,and Cys498 facilitates its extracellular vesicles localization
10.16352/j.issn.1001-6325.2025.09.1151
- VernacularTitle: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
- Author:
Jingjing YANG
1
;
Yan MA
;
Yue WANG
;
Yang SUN
;
Pan LI
;
Feng GUO
Author Information
1. 徐州医科大学 基础医学院 江苏省免疫与代谢重点实验室 病原生物学与免疫学教研室,江苏 徐州 221004
- Keywords:
S-palmitoylation;
multi-site mutagenesis;
post-translational modification;
extra cellular vesicle;
angiotensin-converting enzyme 2(ACE2)
- From:
Basic & Clinical Medicine
2025;45(9):1151-1157
- CountryChina
- Language:Chinese
-
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.
