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

Autor:	Schureck MA; Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, United States., Darling JE; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States., Merk A; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States., Shao J; Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, United States., Daggupati G; Department of Molecular Microbiology and Immunology, and Johns Hopkins Malaria Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States., Srinivasan P; Department of Molecular Microbiology and Immunology, and Johns Hopkins Malaria Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States., Olinares PDB; Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, United States., Rout MP; Laboratory of Cellular and Structural Biology, The Rockefeller University, New York, United States., Chait BT; Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, United States., Wollenberg K; Office of Cyber Infrastructure & Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States., Subramaniam S; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada., Desai SA; Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 Jan 04; Vol. 10. Date of Electronic Publication: 2021 Jan 04.
DOI:	10.7554/eLife.65282
Abstrakt:	Malaria parasites use the RhopH complex for erythrocyte invasion and channel-mediated 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. Competing Interests: MS, JD, AM, JS, GD, PS, PO, MR, BC, KW, SD No competing interests declared, SS Reviewing editor, eLife
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu