Circumsporozoite protein

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Circumsporozoite protein (CSP) is a secreted protein of the sporozoite stage of the malaria parasite (Plasmodium sp.) and is the antigenic target of RTS,S, a pre-erythrocytic malaria vaccine currently undergoing clinical trials.[1] The amino-acid sequence of CSP consists of an immunodominant central repeat region flanked by conserved motifs at the N- and C- termini that are implicated in protein processing as the parasite travels from the mosquito to the mammalian vector.[2]

The structure and function of CSP is highly conserved across the various strains of malaria that infect humans, non-human primates and rodents. It can first be detected in large quantities as sporozoites are forming within oocysts residing in the midgut walls of infected mosquitoes. Upon egression from mature oocysts, sporozoites begin migrating to the salivary glands, and CSP is known to be an important mediator of this process. Additionally, CSP is involved in hepatocyte binding in the mammalian host. Here, the N-terminus and central repeat region initially facilitate parasite binding.[3] On the hepatocyte surface proteolytic cleavage at region 1 of the N-terminus exposes the adhesive domain of the C-terminus, thereby priming the parasites for invasion of the liver.[4]

CSP is an approximately 42 kD soluble protein and can readily be made using an E. coli expression system.

References[edit]

  1. ^ Porter, Michael; Jennifer Nicki; Christopher Pool (June 2013). "Transgenic Parasites Stably Expressing Full-Length Plasmodium falciparum Circumsporozoite Protein as a Model for Vaccine Down-Selection in Mice Using Sterile Protection as an Endpoint". Clinical and Vaccine Immunology. 20 (6): 803–810. doi:10.1128/cvi.00066-13. PMC 3675977.
  2. ^ Aldrich, Cassandra; Alessandro Magini; Carla Emiliani (February 2012). "Roles of the Amino Terminal Region and Repeat Region of the Plasmodium berghei Circumsporozoite Protein in Parasite Infectivity". PLOS ONE. 7 (2): e32524. doi:10.1371/journal.pone.0032524. PMC 3290588. PMID 22393411.
  3. ^ Rathore, Dharmendar; John B. Sacci; Patricia de la Vega; Thomas F. McCutchan (March 2002). "Binding and Invasion of Liver Cells by Plasmodium falciparum Sporozoites". The Journal of Biological Chemistry. 277 (9): 7092–7098. doi:10.1074/jbc.m106862200.
  4. ^ Coppi, Alida; Consuelo Pinzon-Ortiz; Christina Hunter (January 2005). "The Plasmodium circumsporozoite protein is proteolytically processed during cell invasion" (PDF). JEM. 201 (1): 27–33. doi:10.1084/jem.20040989. PMC 1995445.