5OUQ

Structure of TgPLP1 MACPF domain

Summary for 5OUQ

• Entry DOI: 10.2210/pdb5ouq/pdb
• Descriptor: Perforin-like protein 1, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: toxoplasma, cell egress, macpf domain, lipid binding protein
• Biological source: Toxoplasma gondii
• Total number of polymer chains: 6
• Total formula weight: 236003.59

Authors

Ni, T.,Gilbert, R.J.C. (deposition date: 2017-08-24, release date: 2018-04-11, Last modification date: 2024-11-13)

Primary citation

Ni, T.,Williams, S.I.,Rezelj, S.,Anderluh, G.,Harlos, K.,Stansfeld, P.J.,Gilbert, R.J.C.
Structures of monomeric and oligomeric forms of theToxoplasma gondiiperforin-like protein 1.
Sci Adv, 4:eaaq0762-eaaq0762, 2018

PubMed Abstract: and 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 PLP1 (PLP1) 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 PLP1. 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 PLP1.

PubMed: 29750191
DOI: 10.1126/sciadv.aaq0762

Experimental method

X-RAY DIFFRACTION (5.11 Å)