Unknown

Dataset Information

0

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


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 ?-pleated sheet (APC?) domains of TgPLP1. The MACPF domain forms hexameric assemblies, with ring and helix geometries, and the APC? domain has a novel ?-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 APC? 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.

SUBMITTER: Ni T 

PROVIDER: S-EPMC5943054 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

Structures of monomeric and oligomeric forms of the <i>Toxoplasma gondii</i> perforin-like protein 1.

Ni Tao T   Williams Sophie I SI   Rezelj Saša S   Anderluh Gregor G   Harlos Karl K   Stansfeld Phillip J PJ   Gilbert Robert J C RJC  

Science advances 20180321 3


<i>Toxoplasma</i> and <i>Plasmodium</i> 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 <i>Toxoplasma gondii</i> PLP1 (<i>Tg</i>PLP1) 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 <i>Tg</i>PLP1. The  ...[more]

Similar Datasets

| S-EPMC6294395 | biostudies-literature
| S-EPMC8890382 | biostudies-literature
| S-EPMC3346325 | biostudies-literature
| S-EPMC10746232 | biostudies-literature
| S-EPMC2660739 | biostudies-literature
| S-EPMC6857535 | biostudies-literature
| S-EPMC10541014 | biostudies-literature
| S-EPMC2937196 | biostudies-literature
| S-EPMC2042172 | biostudies-literature
| S-EPMC2533231 | biostudies-literature