Malaria parasites use a soluble Rhoph complex for erythrocyte invasion and an integral form for nutrient uptake

Marc A. Schureck, Joseph E. Darling, Alan Merk, Jinfeng Shao, Geervani Daggupati, Prakash Srinivasan, Paul Dominic B. Olinares, Michael P. Rout, Brian T. Chait, Kurt Wollenberg, Sriram Subramaniam, Sanjay A. Desai

Research output: Contribution to journalArticlepeer-review

Abstract

Malaria parasites use the RhopH complex for erythrocyte invasion and channelmediated nutrient uptake. As the member proteins are unique to Plasmodium spp., how they interact and traffic through subcellular sites to serve these essential functions is unknown. We show that RhopH is synthesized as a soluble complex of CLAG3, RhopH2, and RhopH3 with 1:1:1 stoichiometry. After transfer to a new host cell, the complex crosses a vacuolar membrane surrounding the intracellular parasite and becomes integral to the erythrocyte membrane through a PTEX translocon-dependent process. We present a 2.9 Å single-particle cryo-electron microscopy structure of the trafficking complex, revealing that CLAG3 interacts with the other subunits over large surface areas. This soluble complex is tightly assembled with extensive disulfide bonding and predicted transmembrane helices shielded. We propose a large protein complex stabilized for trafficking but poised for host membrane insertion through large-scale rearrangements, paralleling smaller two-state pore-forming proteins in other organisms.

Original languageEnglish (US)
Article numbere65282
Pages (from-to)1-24
Number of pages24
JournaleLife
Volume10
DOIs
StatePublished - Jan 2021

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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