Structural and regulatory insights into the glideosome-associated connector from Toxoplasma gondii

Amit Kumar, Oscar Vadas, Nicolas Dos Santos Pacheco, Xu Zhang, Kin Chao, Nicolas Darvill, Helena Ø Rasmussen, Yingqi Xu, Gloria Meng-Hsuan Lin, Fisentzos A Stylianou, Jan Skov Pedersen, Sarah L Rouse, Marc L Morgan, Dominique Soldati-Favre*, Stephen Matthews*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

2 Citations (Scopus)

Abstract

The phylum of Apicomplexa groups intracellular parasites that employ substrate-dependent gliding motility to invade host cells, egress from the infected cells, and cross biological barriers. The glideosome-associated connector (GAC) is a conserved protein essential to this process. GAC facilitates the association of actin filaments with surface transmembrane adhesins and the efficient transmission of the force generated by myosin translocation of actin to the cell surface substrate. Here, we present the crystal structure of Toxoplasma gondii GAC and reveal a unique, supercoiled armadillo repeat region that adopts a closed ring conformation. Characterisation of the solution properties together with membrane and F-actin binding interfaces suggests that GAC adopts several conformations from closed to open and extended. A multi-conformational model for assembly and regulation of GAC within the glideosome is proposed.

Original languageEnglish
Article numbere86049
JournaleLife
Volume12
Number of pages26
ISSN2050-084X
DOIs
Publication statusPublished - Apr 2023

Keywords

  • Toxoplasma/metabolism
  • Actins/metabolism
  • Actin Cytoskeleton/metabolism
  • Cell Membrane/metabolism
  • Myosins/metabolism
  • Protozoan Proteins/metabolism

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