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Structural, functional and computational studies of membrane recognition by Plasmodium Perforin-Like Proteins 1 and 2
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Williams, Sophie I, Yu, Xiulian, Ni, Tao, Gilbert, Robert J C and Stansfeld, Phillip J. (2022) Structural, functional and computational studies of membrane recognition by Plasmodium Perforin-Like Proteins 1 and 2. Journal of molecular biology, 434 (13). 167642. doi:10.1016/j.jmb.2022.167642 ISSN 1089-8638.
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Official URL: https://doi.org/10.1016/j.jmb.2022.167642
Abstract
Perforin-like proteins (PLPs) play key roles in mechanisms associated with parasitic disease caused by apicomplexans parasites Plasmodium and Toxoplasma. The T. gondii PLP1 (TgPLP1) mediates tachyzoite egress from cells, while the five Plasmodium PLPs carry out various roles in the life cycle of the parasite and with respect to the molecular basis of disease. Here we focus on Plasmodium vivax PLP1 and PLP2 (PvPLP1 and PvPLP2) compared to TgPLP1. Determination of the crystal structure of the membrane-binding APCβ domain of PvPLP1 reveals notable differences with TgPLP1, reflected in its inability to bind lipid bilayers as TgPLP1 and PvPLP2 do. Molecular dynamics simulations combined with site-directed mutagenesis and functional assays allow dissection of the binding interactions of TgPLP1 and PvPLP2 on lipid bilayers, and reveal similar tropisms for lipids enriched in the inner leaflet of the mammalian plasma membrane. In addition PvPLP2 displays a secondary synergistic interaction side-on from its principal bilayer interface. This study underlines the substantial differences between the biophysical properties of the APCβ domains of apicomplexan PLPs, which reflect their significant sequence diversity. Such differences will be important factors in determining the cell targeting and membrane-binding activity of the different proteins in parasitic life cycles and disease.
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, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||||||||
SWORD Depositor: | Library Publications Router | |||||||||||||||
Library of Congress Subject Headings (LCSH): | Molecular dynamics -- Simulation methods, Apicomplexa , Proteins, Proteins -- Biotechnology, Cell membranes, Lipids , Plasmodium , X-ray crystallography | |||||||||||||||
Journal or Publication Title: | Journal of molecular biology | |||||||||||||||
Publisher: | Elsevier | |||||||||||||||
ISSN: | 1089-8638 | |||||||||||||||
Official Date: | 15 July 2022 | |||||||||||||||
Dates: |
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Volume: | 434 | |||||||||||||||
Number: | 13 | |||||||||||||||
Article Number: | 167642 | |||||||||||||||
DOI: | 10.1016/j.jmb.2022.167642 | |||||||||||||||
Status: | Peer Reviewed | |||||||||||||||
Publication Status: | Published | |||||||||||||||
Reuse Statement (publisher, data, author rights): | . | |||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||
Date of first compliant deposit: | 15 July 2022 | |||||||||||||||
Date of first compliant Open Access: | 18 July 2022 | |||||||||||||||
RIOXX Funder/Project Grant: |
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