棕榈酰化
恶性疟原虫
生物
寄生虫寄主
红细胞
膜蛋白
细胞生物学
抗体
抗原
疟疾
生物化学
膜
半胱氨酸
免疫学
酶
万维网
计算机科学
作者
Geeta Kumari,Rex Devasahayam Arokia Balaya,Sangam Giri Goswami,Soumyadeep Mukherjee,Shreeja Biswas,Preeti Maurya,Ravi Jain,Swati Garg,Thottethodi Subrahmanya Keshava Prasad,Soumya Pati,Sivaprakash Ramalingam,Narla Mohandas,Shailja Singh
出处
期刊:ACS Infectious Diseases
[American Chemical Society]
日期:2022-08-31
卷期号:8 (10): 2106-2118
被引量:3
标识
DOI:10.1021/acsinfecdis.2c00199
摘要
Phosphorylation and other post-translational modifications of red blood cell (RBC) proteins govern membrane function and have a role in the invasion of RBCs by the malaria parasite, Plasmodium falciparum. Furthermore, a percentage of RBC proteins are palmitoylated, although the functional consequences are unknown. We establish dynamic palmitoylation of 118 RBC membrane proteins using click chemistry and acyl biotin exchange (ABE)-coupled LC-MS/MS and characterize their involvement in controlling membrane organization and parasite invasion. RBCs were treated with a generic palmitoylation inhibitor, 2-bromopalmitate (2-BMP), and then analyzed using ABE-coupled LC-MS/MS. Only 42 of the 118 palmitoylated proteins detected were palmitoylated in the 2-BMP-treated sample, indicating that palmitoylation is dynamically regulated. Interestingly, membrane receptors such as semaphorin 7A, CR1, and ABCB6, which are known to be involved in merozoite interaction with RBCs and parasite invasion, were found to be dynamically palmitoylated, including the blood group antigen, Kell, whose antigenic abundance was significantly reduced following 2-BMP treatment. To investigate the involvement of Kell in merozoite invasion of RBCs, a specific antibody to its extracellular domain was used. The antibody targeting Kell inhibited merozoite invasion of RBCs by 50%, implying a role of Kell, a dynamically palmitoylated potent host-derived receptor, in parasite invasion. Furthermore, a significant reduction in merozoite contact with the RBC membrane and a consequent decrease in parasite invasion following 2-BMP treatment demonstrated that palmitoylation does indeed regulate RBC susceptibility to parasite invasion. Taken together, our findings revealed the dynamic palmitoylome of RBC membrane proteins and its role in P. falciparum invasion.
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