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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DOI：
10.7554/elife.86049
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发表时间：
2023-04-04
期刊：
影响因子：
7.7
通讯作者：
Matthews S
中科院分区：
文献类型：
--
作者：
Kumar A;Vadas O;Dos Santos Pacheco N;Zhang X;Chao K;Darvill N;Rasmussen HØ;Xu Y;Lin GM;Stylianou FA;Pedersen JS;Rouse SL;Morgan ML;Soldati-Favre D;Matthews S
Apicomplexa门将细胞内的寄生虫归类，这些寄生虫利用底物依赖的滑动运动入侵宿主细胞，从感染的细胞中排出，并跨越生物屏障。胶质小体相关连接蛋白(GAC)是一种在这一过程中必不可少的保守蛋白质。GAC促进肌动蛋白细丝与表面跨膜粘附素的结合，并将肌球蛋白转位所产生的力有效地传递到细胞表面底物。在这里，我们介绍了弓形虫GAC的晶体结构，并揭示了一个独特的、采用闭合环状构象的超螺旋犰螈重复区域。对溶液性质以及膜和F-肌动蛋白结合界面的表征表明，GAC具有从闭合到开放和延伸的几种构象。提出了GAC在胶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.