Protein Prenylation and Hsp40 in Thermotolerance of Plasmodium falciparum Malaria Parasites

mBio. 2021 Jun 29;12(3):e0076021. doi: 10.1128/mBio.00760-21. Epub 2021 Jun 29.


During its complex life cycle, the malaria parasite survives dramatic environmental stresses, including large temperature shifts. Protein prenylation is required during asexual replication of Plasmodium falciparum, and the canonical heat shock protein 40 protein (HSP40; PF3D7_1437900) is posttranslationally modified with a 15-carbon farnesyl isoprenyl group. In other organisms, farnesylation of Hsp40 orthologs controls their localization and function in resisting environmental stress. In this work, we find that plastidial isopentenyl pyrophosphate (IPP) synthesis and protein farnesylation are required for malaria parasite survival after cold and heat shock. Furthermore, loss of HSP40 farnesylation alters its membrane attachment and interaction with proteins in essential pathways in the parasite. Together, this work reveals that farnesylation is essential for parasite survival during temperature stress. Farnesylation of HSP40 may promote thermotolerance by guiding distinct chaperone-client protein interactions.

Keywords: Plasmodium falciparum; farnesylation; heat shock; isoprenoids; malaria; protein chaperone.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Erythrocytes / parasitology
  • HSP40 Heat-Shock Proteins / genetics
  • HSP40 Heat-Shock Proteins / metabolism*
  • Heat-Shock Response
  • Hemiterpenes / metabolism
  • Host-Parasite Interactions
  • Humans
  • Life Cycle Stages
  • Organophosphorus Compounds / metabolism
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / metabolism*
  • Protein Prenylation*
  • Protozoan Proteins / genetics
  • Thermotolerance*


  • HSP40 Heat-Shock Proteins
  • Hemiterpenes
  • Organophosphorus Compounds
  • Protozoan Proteins
  • isopentenyl pyrophosphate