气候变化领域集成服务门户(CCPortal): Complement C1s cleaves PfEMP1 at interdomain conserved sites inhibiting Plasmodium falciparum cytoadherence

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DOI	10.1073/pnas.2104166118
	Complement C1s cleaves PfEMP1 at interdomain conserved sites inhibiting Plasmodium falciparum cytoadherence
	Azasi Y.; Low L.M.; Just A.N.; Raghavan S.S.R.; Wang C.W.; Valenzuela-Leon P.; Alexandra Rowe J.; Smith J.D.; Lavstsen T.; Turner L.; Calvo E.; Miller L.H.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:22
英文摘要	Cytoadhesion of Plasmodium falciparum-infected erythrocytes (IEs) to the endothelial lining of blood vessels protects parasites from splenic destruction, but also leads to detrimental inflammation and vessel occlusion. Surface display of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion ligands exposes them to host antibodies and serum proteins. PfEMP1 are important targets of acquired immunity to malaria, and through evolution, the protein family has expanded and diversified to bind a select set of host receptors through antigenically diversified receptor-binding domains. Here, we show that complement component 1s (C1s) in serum cleaves PfEMP1 at semiconserved arginine motifs located at interdomain regions between the receptor-binding domains, rendering the IE incapable of binding the two main PfEMP1 receptors, CD36 and endothelial protein C receptor (EPCR). Bioinformatic analyses of PfEMP1 protein sequences from 15 P. falciparum genomes found the C1s motif was present in most PfEMP1 variants. Prediction of C1s cleavage and loss of binding to endothelial receptors was further corroborated by testing of several different parasite lines. These observations suggest that the parasites have maintained susceptibility for cleavage by the serine protease, C1s, and provides evidence for a complex relationship between the complement system and the P. falciparum cytoadhesion virulence determinant. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	C1s; Cytoadhesion; EPCR; Malaria; PfEMP1
语种	英语
scopus关键词	CD36 antigen; complement component C1s; endothelial protein C receptor; erythrocyte membrane protein 1; amino terminal sequence; Article; bioinformatics; cell adhesion; controlled study; enzyme inhibition; fractionation; genotype; high performance liquid chromatography; human; human cell; liquid chromatography-mass spectrometry; nonhuman; parasite virulence; Plasmodium falciparum; prediction; protein cleavage; protein expression; protein motif; protein targeting; real time polymerase chain reaction; receptor binding
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238904
作者单位	Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, United States; Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, 2200, Denmark; Department of Infectious Diseases, Rigshospitalet, Copenhagen, 2100, Denmark; Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, EH9 3FL, United Kingdom; Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FL, United Kingdom; Center for Global Infectious Disease Resesarch, Seattle Children’s Research Institute, Seattle, WA 98109, United States; Department of Pediatrics, University of Washington, Seattle, WA 98195, United States; Department of Global Health, University of Washington, Seattle, WA 98195, United States
推荐引用方式 GB/T 7714	Azasi Y.,Low L.M.,Just A.N.,et al. Complement C1s cleaves PfEMP1 at interdomain conserved sites inhibiting Plasmodium falciparum cytoadherence[J],2021,118(22).
APA	Azasi Y..,Low L.M..,Just A.N..,Raghavan S.S.R..,Wang C.W..,...&Miller L.H..(2021).Complement C1s cleaves PfEMP1 at interdomain conserved sites inhibiting Plasmodium falciparum cytoadherence.Proceedings of the National Academy of Sciences of the United States of America,118(22).
MLA	Azasi Y.,et al."Complement C1s cleaves PfEMP1 at interdomain conserved sites inhibiting Plasmodium falciparum cytoadherence".Proceedings of the National Academy of Sciences of the United States of America 118.22(2021).