Structure of the Plasmodium-interspersed repeat proteins of the malaria parasite

DOI: 10.1073/pnas.2016775117

Authors: Thomas E. Harrison (University of Oxford) , Adam J. Reid (Wellcome Sanger Institute) , Deirdre Cunningham (The Francis Crick Institute) , Jean Langhorne (The Francis Crick Institute) , Matthew Higgins (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Proceedings Of The National Academy Of Sciences , VOL 1

State: Published (Approved)
Published: November 2020
Diamond Proposal Number(s): 23459

Abstract: 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.

Subject Areas: Biology and Bio-materials


Instruments: I23-Long wavelength MX

Documents:
32098.full.pdf