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.
journal_name
Proc Natl Acad Sci U S Aauthors
Harrison TE,Reid AJ,Cunningham D,Langhorne J,Higgins MKdoi
10.1073/pnas.2016775117subject
Has Abstractpub_date
2020-12-15 00:00:00pages
32098-32104issue
50eissn
0027-8424issn
1091-6490pii
2016775117journal_volume
117pub_type
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