Structures of monomeric and oligomeric forms of the Toxoplasma gondii perforin-like protein 1.

Science Advances
Tao NiRobert Gilbert

Abstract

Toxoplasma and Plasmodium are the parasitic agents of toxoplasmosis and malaria, respectively, and use perforin-like proteins (PLPs) to invade host organisms and complete their life cycles. The Toxoplasma gondii PLP1 (TgPLP1) is required for efficient exit from parasitophorous vacuoles in which proliferation occurs. We report structures of the membrane attack complex/perforin (MACPF) and Apicomplexan PLP C-terminal β-pleated sheet (APCβ) domains of TgPLP1. The MACPF domain forms hexameric assemblies, with ring and helix geometries, and the APCβ domain has a novel β-prism fold joined to the MACPF domain by a short linker. Molecular dynamics simulations suggest that the helical MACPF oligomer preserves a biologically important interface, whereas the APCβ domain binds preferentially through a hydrophobic loop to membrane phosphatidylethanolamine, enhanced by the additional presence of inositol phosphate lipids. This mode of membrane binding is supported by site-directed mutagenesis data from a liposome-based assay. Together, these structural and biophysical findings provide insights into the molecular mechanism of membrane targeting by TgPLP1.

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Citations

Apr 9, 2020·Frontiers in Cellular and Infection Microbiology·Swati GargShailja Singh
Sep 21, 2019·Nature Communications·Siew Siew PangJames C Whisstock
Oct 13, 2020·Frontiers in Cellular and Infection Microbiology·Juliane SassmannshausenSandra Bennink

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Methods Mentioned

BETA
electrophoresis
x-ray scattering
glycosylation
transfection
size-exclusion chromatography
electron
electron microscopy
chips

Software Mentioned

HOLE
Coot
refine
ProFit
ATSAS
phenix
PyMOL Molecular Graphics System
Gromacs
VMD
AutoRg

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