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Allosteric regulation controls actin-bundling properties of human plastins
Nature Structural & Molecular Biology ( IF 16.8 ) Pub Date : 2022-05-19 , DOI: 10.1038/s41594-022-00771-1
Christopher L Schwebach 1 , Elena Kudryashova 1 , Richa Agrawal 1, 2 , Weili Zheng 3, 4 , Edward H Egelman 3 , Dmitri S Kudryashov 1
Affiliation  

Plastins/fimbrins are conserved actin-bundling proteins contributing to motility, cytokinesis and other cellular processes by organizing strikingly different actin assemblies as in aligned bundles and branched networks. We propose that this ability of human plastins stems from an allosteric communication between their actin-binding domains (ABD1/2) engaged in a tight spatial association. Here we show that ABD2 can bind actin three orders of magnitude stronger than ABD1, unless the domains are involved in an equally strong inhibitory engagement. A mutation mimicking physiologically relevant phosphorylation at the ABD1–ABD2 interface greatly weakened their association, dramatically potentiating actin cross-linking. Cryo-EM reconstruction revealed the ABD1–actin interface and enabled modeling of the plastin bridge and domain separation in parallel bundles. We predict that a strong and tunable allosteric inhibition between the domains allows plastins to modulate the cross-linking strength, contributing to remodeling of actin assemblies of different morphologies defining the unique place of plastins in actin organization.



中文翻译:

变构调节控制人塑化蛋白的肌动蛋白结合特性

Plastins/fimbrins 是保守的肌动蛋白捆绑蛋白,通过组织显着不同的肌动蛋白组装,如对齐束和分支网络,有助于运动、胞质分裂和其他细胞过程。我们提出,人类 plastins 的这种能力源于其肌动蛋白结合域 (ABD1/2) 之间的变构通信,这些结构域具有紧密的空间关联。在这里,我们表明 ABD2 可以结合比 ABD1 强三个数量级的肌动蛋白,除非这些域参与同样强烈的抑制作用。在 ABD1-ABD2 界面模拟生理相关磷酸化的突变大大削弱了它们的结合,显着增强了肌动蛋白交联。Cryo-EM 重建揭示了 ABD1-肌动蛋白界面,并启用了平行束中的塑蛋白桥和域分离的建模。我们预测,域之间强大且可调的变构抑制允许 plastins 调节交联强度,有助于重塑不同形态的肌动蛋白组件,定义 plastins 在肌动蛋白组织中的独特位置。

更新日期:2022-05-20
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