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

doi:10.7554/eLife.86049

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 af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

3 Citationer (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.

Originalsprog	Engelsk
Artikelnummer	e86049
Tidsskrift	eLife
Vol/bind	12
Antal sider	26
ISSN	2050-084X
DOI	https://doi.org/10.7554/eLife.86049
Status	Udgivet - apr. 2023

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10.7554/eLife.86049Licens: CC BY

Citationsformater

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. (2023). Structural and regulatory insights into the glideosome-associated connector from Toxoplasma gondii. eLife, 12, Artikel e86049. https://doi.org/10.7554/eLife.86049

@article{882484a351a44027b7cce5abd3338998,

title = "Structural and regulatory insights into the glideosome-associated connector from Toxoplasma gondii",

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.",

keywords = "Actin Cytoskeleton/metabolism, Actins/metabolism, Cell Membrane/metabolism, Myosins/metabolism, Protozoan Proteins/metabolism, Toxoplasma/metabolism",

author = "Amit Kumar and Oscar Vadas and {Dos Santos Pacheco}, Nicolas and Xu Zhang and Kin Chao and Nicolas Darvill and Rasmussen, {Helena {\O}} and Yingqi Xu and Lin, {Gloria Meng-Hsuan} and Stylianou, {Fisentzos A} and Pedersen, {Jan Skov} and Rouse, {Sarah L} and Morgan, {Marc L} and Dominique Soldati-Favre and Stephen Matthews",

note = "{\textcopyright} 2023, Kumar et al.",

year = "2023",

month = apr,

doi = "10.7554/eLife.86049",

language = "English",

volume = "12",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

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TY - JOUR

T1 - Structural and regulatory insights into the glideosome-associated connector from Toxoplasma gondii

AU - Kumar, Amit

AU - Vadas, Oscar

AU - Dos Santos Pacheco, Nicolas

AU - Zhang, Xu

AU - Chao, Kin

AU - Darvill, Nicolas

AU - Rasmussen, Helena Ø

AU - Xu, Yingqi

AU - Lin, Gloria Meng-Hsuan

AU - Stylianou, Fisentzos A

AU - Pedersen, Jan Skov

AU - Rouse, Sarah L

AU - Morgan, Marc L

AU - Soldati-Favre, Dominique

AU - Matthews, Stephen

PY - 2023/4

Y1 - 2023/4

N2 - 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.

AB - 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.

KW - Actin Cytoskeleton/metabolism

KW - Actins/metabolism

KW - Cell Membrane/metabolism

KW - Myosins/metabolism

KW - Protozoan Proteins/metabolism

KW - Toxoplasma/metabolism

U2 - 10.7554/eLife.86049

DO - 10.7554/eLife.86049

M3 - Journal article

C2 - 37014051

SN - 2050-084X

VL - 12

JO - eLife

JF - eLife

M1 - e86049

ER -

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

Abstract

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