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Structures of monomeric and oligomeric forms of the Toxoplasma gondiiperforin-like protein 1
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Ni, Tao, Williams, Sophie I., Rezelj, Saša, Anderluh, Gregor, Harlos, Karl, Stansfeld, Phillip J. and Gilbert, Robert J. C. (2018) Structures of monomeric and oligomeric forms of the Toxoplasma gondiiperforin-like protein 1. Science Advances, 4 (3). eaaq0762. doi:10.1126/sciadv.aaq0762
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Official URL: http://dx.doi.org/10.1126/sciadv.aaq0762
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.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||
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| Subjects: | Q Science > QL Zoology Q Science > QP Physiology |
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| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||||||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Toxoplasma gondii, Plasmodium, Proteins | ||||||||||||||||||||||||||||||
| Journal or Publication Title: | Science Advances | ||||||||||||||||||||||||||||||
| Publisher: | American Association for the Advancement of Science | ||||||||||||||||||||||||||||||
| ISSN: | 2375-2548 | ||||||||||||||||||||||||||||||
| Official Date: | 2 March 2018 | ||||||||||||||||||||||||||||||
| Dates: |
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| Date of first compliant deposit: | 11 November 2019 | ||||||||||||||||||||||||||||||
| Volume: | 4 | ||||||||||||||||||||||||||||||
| Number: | 3 | ||||||||||||||||||||||||||||||
| Article Number: | eaaq0762 | ||||||||||||||||||||||||||||||
| DOI: | 10.1126/sciadv.aaq0762 | ||||||||||||||||||||||||||||||
| Status: | Peer Reviewed | ||||||||||||||||||||||||||||||
| Publication Status: | Published | ||||||||||||||||||||||||||||||
| Access rights to Published version: | Open Access | ||||||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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