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

DOI: 10.1126/sciadv.aaq0762 DOI Help

Authors: Tao Ni (University of Oxford) , Sophie I. Williams (University of Oxford) , Saša Rezelj (National Institute of Chemistry, Slovenia) , Gregor Anderluh (National Institute of Chemistry, Slovenia) , Karl Harlos (Wellcome Trust Centre for Human Genetics, University of Oxford) , Phillip J. Stansfeld (University of Oxford) , Robert J. C. Gilbert (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science Advances , VOL 4

State: Published (Approved)
Published: March 2018
Diamond Proposal Number(s): 10627

Open Access Open Access

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.

Diamond Keywords: Malaria; Toxoplasmosis

Subject Areas: Biology and Bio-materials

Instruments: I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Added On: 28/03/2018 09:10


Discipline Tags:

Infectious Diseases Disease in the Developing World Health & Wellbeing Structural biology Biophysics Life Sciences & Biotech Parasitology

Technical Tags:

Diffraction Macromolecular Crystallography (MX)