Plasmodium falciparum circumsporozoite protein - C-terminal thrombospondin-like type I repeat domain (PfCSP-TSR)

The Plasmodium falciparum circumsporozoite protein (PfCSP) is the most abundant surface protein on the sporozoite stage of the malaria parasite and is essential for its development and infectivity. The C-terminal thrombospondin-like type I repeat (TSR) domain is a highly structured region of PfCSP that mediates the critical step of parasite attachment to heparan sulfate proteoglycans on the surface of host hepatocytes (UniProt P04924). This domain contains both conserved structural motifs required for cell invasion and important T-cell epitopes that contribute to the protective immune response (Scally et al., 2018, Science). As a primary component of the WHO-approved RTS,S/AS01 and R21/Matrix-M vaccines, the C-terminal TSR domain is targeted to elicit neutralizing antibodies that prevent the parasite from establishing a liver-stage infection (Datoo et al., 2021, The Lancet). Research into monoclonal antibodies targeting this domain has also shown promise in providing passive immunity against malaria (Kisalu et al., 2018, Nature Medicine). Understanding the structural biology and polymorphism of the C-terminal TSR is vital for the design of next-generation malaria vaccines and therapeutics.

Other names

PfCSP C-terminal domainCircumsporozoite surface protein C-terminusalpha-TSR domain of PfCSPC-TSR

Induction of humoral and cellular immune responses to block sporozoite invasion of hepatocytes and inhibit the pre-erythrocytic stage of the malaria parasite life cycle.