Toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover.
Toxoplasma gondii actin filaments are tuned for rapid disassembly and turnover.
复制标题
弓形虫肌动蛋白丝经过调整，可快速拆卸和周转。
DOI：
10.1101/2023.08.29.555340
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Heaslip,AoifeT
中科院分区：
文献类型：
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作者：
Hvorecny,KelliL;Sladewski,ThomasE;DeLaCruz,EnriqueM;Kollman,JustinM;Heaslip,AoifeT
细胞骨架蛋白肌动蛋白在细胞内寄生虫弓形虫的致病性中起关键作用，介导侵入和外出，货物运输和细胞器遗传。活细胞成像的进展揭示了广泛的丝状肌动蛋白网络的顶复门寄生虫，但有相互矛盾的数据有关的生化和生物物理特性ofToxoplasmaactin。在这里，我们对体外组装的单个弓形虫肌动蛋白细丝进行了真实的成像，显示出天然的、不稳定的细丝长度为数十微米。与骨骼肌肌动蛋白不同，弓形虫微丝由于高临界浓度、快速单体解离和快速核苷酸交换而固有地经历快速螺旋研磨。jasplakinolide稳定的和天然的（即不稳定的）细丝的冷冻-EM结构显示出类似骨架肌动蛋白的结构，在D环中组装接触的差异解释了细丝的动态性质，这可能是顶复门肌动蛋白的保守特征。这项工作表明，在组装界面的进化变化可以调整肌动蛋白丝的动态特性，而不破坏其保守的结构。
The cytoskeletal protein actin plays a critical role in the pathogenicity of the intracellular parasite,Toxoplasma gondii, mediating invasion and egress, cargo transport, and organelle inheritance. Advances in live cell imaging have revealed extensive filamentous actin networks in the Apicomplexan parasite, but there are conflicting data regarding the biochemical and biophysical properties ofToxoplasmaactin. Here, we imaged the in vitro assembly of individualToxoplasmaactin filaments in real time, showing that native, unstabilized filaments grow tens of microns in length. Unlike skeletal muscle actin,Toxoplasmafilaments intrinsically undergo rapid treadmilling due to a high critical concentration, fast monomer dissociation, and rapid nucleotide exchange. Cryo-EM structures of jasplakinolide-stabilized and native (i.e. unstabilized) filaments show an architecture like skeletal actin, with differences in assembly contacts in the D-loop that explain the dynamic nature of the filament, likely a conserved feature of Apicomplexan actin. This work demonstrates that evolutionary changes at assembly interfaces can tune the dynamic properties of actin filaments without disrupting their conserved structure.