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

Structural and regulatory insights into the glideosome-associated connector from Toxoplasma gondii
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对弓形虫滑翔体相关连接器的结构和监管见解

DOI:
10.1101/2023.01.23.525158
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发表时间:
2023
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通讯作者:
Kumar A
Kumar A
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--
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作者:
Kumar A

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顶复门(Apicomplexa)是一种细胞内寄生虫,它们利用底物依赖性的滑动运动侵入宿主细胞,从受感染的细胞中排出,并穿过生物屏障。滑动体相关连接器(GAC)是该过程所必需的保守蛋白。GAC促进肌动蛋白丝与表面跨膜粘附素的结合,并促进肌动蛋白的肌球蛋白易位到细胞表面底物所产生的力的有效传递。在这里,我们提出了弓形虫GAC的晶体结构,并揭示了一个独特的,超螺旋的犰狳重复区,采用闭环构象。表征的溶液性质与膜和F-肌动蛋白结合界面表明,GAC采用几种构象从封闭到开放和扩展。提出了GAC在滑体内组装和调控的多构象模型。
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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