Circumsporozoite (CS) Protein Sequence

Definition
Circumsporozoite (CS) protein is an antigen present on sporozoite cell surface that is characterized by conserved tandem repeats in their central region1. They are known to be a major target of host immune response1.

Discovery
CS protein was first identified in 1980 when antibodies from fused plasmocytoma cells/murine spleen cells could bind to a protein (now known as CS) on the cell surface of sporozoites2.

Classification
The CS protein belongs to the Thrombospondin-related Protein Family of Apicomplexan Parasites3.

Structural Characteristics
All CS proteins possess a signal sequence at the N-terminus and a hydrophobic sequence at their C-terminus4. In the center is a relatively conserved region of tandem repeats that considerably differs in length, sequence and number depending on the species4. This repetitive region serves as an immunodominant epitope4.

Mode of action
Upon cell contact the sporozoite translocates the CS protein by an unknown mechanism into the cytosol of the cell5. It then spreads throughout the cytosol and binds to cytoplasmic and endoplasmic ribosomes and hence controls protein synthesis in the host cell5.

Functions
CS protein is the major target for host immune response6. The repetitive epitopes of the CS protein are candidates for developing a vaccine against malaria6.

References
1.Schofield L (1990). The circumsporozoite protein of Plasmodium: a mechanism of immune evasion by the malaria parasite? Bull World Health Organ, 68, 66-73.
2.Yoshida N, Nussenzweig RS, Potocnjak P, Nussenzweig V, Aikawa M (1980). Hybridoma produces protective antibodies directed against the sporozoite stage of malaria parasite. Science, 207(4426), 71-3.
3.Naitza S, Spano F, Robson KJH and Crisant A (1998). The Thrombospondin-related Protein Family of Apicomplexan Parasites: The Gears of the Cell Invasion Machinery. Parasitology Today, 14 (12), 479-484.
4.Book: Advances in Parasitology, John R. Baker, R. Mulle, 81-83.
5.Frevert U, Galinski MR, Hügel FU, Allon N, Schreier H, Smulevitch S, Shakibaei M, and Clavijo P (1998). Malaria circumsporozoite protein inhibits protein synthesis in mammalian cells. EMBO J, 17(14), 3816–3826.
6.Del Giudice G, Tougne C, Louis JA, Lambert PH, Bianchi E, Bonelli F, Chiappinelli L, Pessi A (2005). A multiple antigen peptide from the repetitive sequence of the Plasmodium malariae circumsporozoite protein induces a specific antibody response in mice of various H-2 haplotypes. Euro J of Immunol., 20 (7), 1619-1622.