Structural and regulatory insights into the glideosome-associated connector from Toxoplasma gondii
Open accessPublished version of a preprint
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.
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Cites
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- Authors
- Kumar, A., Vadas, O., Dos Santos Pacheco, N., Zhang, X., Chao, K., Darvill, N., Rasmussen, H. Ø., Xu, Y., Lin, G. M.-H., Stylianou, F. A., Pedersen, J. S., Rouse, S. L., Morgan, M. L., Soldati-Favre, D., & Matthews, S.
- Affiliations
- Imperial College London (GB)
- University of Geneva (CH)
- Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva
- Aarhus University (DK)
- Corresponding author
- Matthews, Stephen
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2023-04-04
- Volume
- 12
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC10125020
- OpenAlex
- W4362520906
- Cited by
- 15
- References
- 4
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 4 · 2023: 3
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Leverhulme Trust (RPG_2018_107)
- Biotechnology and Biological Sciences Research Council (BB/W001764/1, BB/D524840/1)
- Swiss Re Foundation (10030_185325, CRSII5_198545)
- Wellcome Trust (202926/Z/16/Z)
- Independent Research Fund Denmark (8021-00133B)
- Topics
- Life Sciences › Immunology and Microbiology › Parasitology › Toxoplasma gondii Research Studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Coccidia and coccidiosis research
- Keywords
- Toxoplasma gondii, gliding motility, armadillo repeats, protein crystal structure, actin binding, membrane binding, Apicomplexa
- MeSH terms
- Actins, Cell Membrane, Actin Cytoskeleton, Myosins, Toxoplasma, Protozoan Proteins
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