Journal article
Structures of monomeric and oligomeric forms of the Toxoplasma gondii perforin-like protein 1
- Abstract:
- Copyright © 2018 The Authors, some rights reserved. Toxoplasma and Plasmodium are the parasitic agents of toxoplasmosis and malaria, respectively, and use perforinlike 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 b-pleated sheet (APCb) domains of TgPLP1. The MACPF domain forms hexameric assemblies, with ring and helix geometries, and the APCb domain has a novel b-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 APCb 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.1MB, Terms of use)
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- Publisher copy:
- 10.1126/sciadv.aaq0762
Authors
+ Slovenian Research Agency
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- Funding agency for:
- Rezelj, S
- Anderluh, G
- Grant:
- P1-0391
- P1-0391
+ Biotechnology and Biological Sciences Research Council
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- Funding agency for:
- Williams, S
- Grant:
- BB/M011224/1
- BB/R002517/1
+ Medical Research Council
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- Funding agency for:
- Williams, S
- Grant:
- BB/M011224/1
+ Chinese Scholarships Council–University of Oxford scholar
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- Funding agency for:
- Ni, T
- Publisher:
- American Association for the Advancement of Science
- Journal:
- Science Advances More from this journal
- Volume:
- 4
- Issue:
- 3
- Article number:
- eaaq0762
- Publication date:
- 2018-03-21
- Acceptance date:
- 2018-02-09
- DOI:
- ISSN:
-
2375-2548
- Keywords:
- Pubs id:
-
pubs:833617
- UUID:
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uuid:9499dc1f-82ec-4bb6-badf-27ab8d6ac7e4
- Local pid:
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pubs:833617
- Source identifiers:
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833617
- Deposit date:
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2018-04-08
Terms of use
- Copyright holder:
- © 2018 Ni, et al
- Copyright date:
- 2018
- Notes:
-
Distributed under a Creative Commons Attribution License 4.0 (CC BY).
This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Licence:
- CC Attribution (CC BY)
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