Identification and analysis of a novel scavenger receptor-like protein conserved in Plasmodium species

Eriksdotter Waller, Cecilia Caroline (2004). Identification and analysis of a novel scavenger receptor-like protein conserved in Plasmodium species. PhD thesis The Open University.



In October 2002, the complete sequence of the genome of the human malaria parasite Plasmodium falciparum was published. The data showed that as many as 60% of all identified open reading frames were unique to the parasite, with no known homologues in other species. Identification and characterization of novel molecules that may provide targets for drug and vaccine design is crucial to fight malaria.

The aim of this project has been to analyse a novel gene and protein in Plasmodium. A short nucleotide fragment was originally identified in Plasmodium chabaudi chabaudi (AS) and the complete sequence subsequently obtained using Vectorette PCR. A singleexon gene was identified and Southern analysis showed the presence of a single copy in the P. chabaudi genome. Analysis of the protein secondary structure revealed a multidomain molecule consisting of an N-terminal secretion signal, two Scavenger Receptor Cysteine-Rich (SRCR) domains, three Limulus factor C, Coch-5b2 and Lgl1 (LCCL) modules and an LH2/PLAT domain. These motifs all have adhesive properties, and the protein was subsequently named Plasmodium SRCR LCCL Adhesive-like Protein (PSLAP).

Multiple sequence alignment established that PSLAP is highly conserved within Plasmodium and also identified a paralogue in Toxoplasma gondii, suggesting it may play a specific and vital role in apicomplexan biology. Results from indirect immunofluoresence assays showed a punctate expression pattern contained within the parasite, indicating that the protein is distributed in vesicles. Northern analysis and immunofluorescence co-localisation studies showed transcription and expression in blood-stage gametocytes, demonstrating that PSLAP is a sexual stage protein.

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