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

TitleStructures of monomeric and oligomeric forms of the Toxoplasma gondii perforin-like protein 1
Authors
Issue Date2018
Citation
Science Advances, 2018, v. 4, n. 3, article no. eaaq0762 How to Cite?
AbstractToxoplasma 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.
Persistent Identifierhttp://hdl.handle.net/10722/316492
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorNi, Tao-
dc.contributor.authorWilliams, Sophie I.-
dc.contributor.authorRezelj, Saša-
dc.contributor.authorAnderluh, Gregor-
dc.contributor.authorHarlos, Karl-
dc.contributor.authorStansfeld, Phillip J.-
dc.contributor.authorGilbert, Robert J.C.-
dc.date.accessioned2022-09-14T11:40:34Z-
dc.date.available2022-09-14T11:40:34Z-
dc.date.issued2018-
dc.identifier.citationScience Advances, 2018, v. 4, n. 3, article no. eaaq0762-
dc.identifier.urihttp://hdl.handle.net/10722/316492-
dc.description.abstractToxoplasma 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.-
dc.languageeng-
dc.relation.ispartofScience Advances-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleStructures of monomeric and oligomeric forms of the Toxoplasma gondii perforin-like protein 1-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1126/sciadv.aaq0762-
dc.identifier.pmid29750191-
dc.identifier.pmcidPMC5943054-
dc.identifier.scopuseid_2-s2.0-85044373907-
dc.identifier.volume4-
dc.identifier.issue3-
dc.identifier.spagearticle no. eaaq0762-
dc.identifier.epagearticle no. eaaq0762-
dc.identifier.eissn2375-2548-
dc.identifier.isiWOS:000431373300023-

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