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

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 tha...

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Autores principales: Harrison, Thomas E., Reid, Adam J., Cunningham, Deirdre, Langhorne, Jean, Higgins, Matthew K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749308/
https://www.ncbi.nlm.nih.gov/pubmed/33257570
http://dx.doi.org/10.1073/pnas.2016775117
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author Harrison, Thomas E.
Reid, Adam J.
Cunningham, Deirdre
Langhorne, Jean
Higgins, Matthew K.
author_facet Harrison, Thomas E.
Reid, Adam J.
Cunningham, Deirdre
Langhorne, Jean
Higgins, Matthew K.
author_sort Harrison, Thomas E.
collection PubMed
description 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.
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spelling pubmed-77493082020-12-24 Structure of the Plasmodium-interspersed repeat proteins of the malaria parasite Harrison, Thomas E. Reid, Adam J. Cunningham, Deirdre Langhorne, Jean Higgins, Matthew K. Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2020-12-15 2020-11-30 /pmc/articles/PMC7749308/ /pubmed/33257570 http://dx.doi.org/10.1073/pnas.2016775117 Text en Copyright © 2020 the Author(s). Published by PNAS. http://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biological Sciences
Harrison, Thomas E.
Reid, Adam J.
Cunningham, Deirdre
Langhorne, Jean
Higgins, Matthew K.
Structure of the Plasmodium-interspersed repeat proteins of the malaria parasite
title Structure of the Plasmodium-interspersed repeat proteins of the malaria parasite
title_full Structure of the Plasmodium-interspersed repeat proteins of the malaria parasite
title_fullStr Structure of the Plasmodium-interspersed repeat proteins of the malaria parasite
title_full_unstemmed Structure of the Plasmodium-interspersed repeat proteins of the malaria parasite
title_short Structure of the Plasmodium-interspersed repeat proteins of the malaria parasite
title_sort structure of the plasmodium-interspersed repeat proteins of the malaria parasite
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749308/
https://www.ncbi.nlm.nih.gov/pubmed/33257570
http://dx.doi.org/10.1073/pnas.2016775117
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