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Publication Abstract from PubMed

The deadly symptoms of malaria occur as Plasmodium parasites replicate within blood cells. Members of several variant surface protein families are expressed on infected blood cell surfaces. Of these, the largest and most ubiquitous are the Plasmodium-interspersed repeat (PIR) proteins, with more than 1,000 variants in some genomes. Their functions are mysterious, but differential pir gene expression associates with acute or chronic infection in a mouse malaria model. The membership of the PIR superfamily, and whether the family includes Plasmodium falciparum variant surface proteins, such as RIFINs and STEVORs, is controversial. Here we reveal the structure of the extracellular domain of a PIR from Plasmodium chabaudi We use structure-guided sequence analysis and molecular modeling to show that this fold is found across PIR proteins from mouse- and human-infective malaria parasites. Moreover, we show that RIFINs and STEVORs are not PIRs. This study provides a structure-guided definition of the PIRs and a molecular framework to understand their evolution.

Structure of the Plasmodium-interspersed repeat proteins of the malaria parasite.,Harrison TE, Reid AJ, Cunningham D, Langhorne J, Higgins MK Proc Natl Acad Sci U S A. 2020 Dec 15;117(50):32098-32104. doi:, 10.1073/pnas.2016775117. Epub 2020 Nov 30. PMID:33257570^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.