• Vesicle Prep Pro

    市场上第一款全自动制备无溶剂巨型单层囊泡(GUVs)的设备
  • Vesicle Prep Pro

    GUVs大小一致-适用与不同的应用

2018 - Structures of monomeric and oligomeric forms of the Toxoplasma gondii perforin-like protein 1

Icon Orbit Mini   Orbit mini and   icon vpp   Vesicle Prep Pro publication in Science Advances (2018)

Authors:
Ni T., Williams S.I., Rezelj S., Anderluh G., Harlos K., Stansfeld P.J., Gilbert R.J.C.

Journal:
Science Advances (2018) 4(3):eaaq0762


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.


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