MglA functions as a three-state GTPase to control movement reversals of Myxococcus xanthus
MglA functions as a three-state GTPase to control movement reversals of Myxococcus xanthus
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DOI：
10.1038/s41467-019-13274-3
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发表时间：
2019-11-22
影响因子：
16.6
通讯作者：
Cherfils, Jacqueline
中科院分区：
文献类型：
--
作者：
Galicia, Christian;Lhospice, Sebastien;Cherfils, Jacqueline
在黄色粘球菌中，定向运动是由小GTdR MglA及其GAP MglB的极间振荡控制的。方向反转需要MglA被MglB失活，然而矛盾的是，MglA和MglB在反转起始时位于相反的两极。在这里，我们报告了完整的MglA/MglB结构循环，结合GAP动力学和体内运动性测定，揭示了MglA是一种三态GTPase，并提出了协调MglA/MglB重新定位的分子机制。我们表明，MglA具有一个非典型的GTP结合状态（MglA-GTP*），这是难治性MglB，并重新敏化由MglA-GDP操作的反馈机制。通过鉴定和突变MglB的极点结合区，我们提供了体内存在MglA-GTP* 状态的证据。这些数据支持这样的模型，其中MglA-GDP充当可溶性信使以将极性MglA-GTP* 转化成可扩散的MglA-GTP种类，其在逆转期间重新定位到相反的极。
In Myxococcus xanthus, directed movement is controlled by pole-to-pole oscillations of the small GTPase MglA and its GAP MglB. Direction reversals require that MglA is inactivated by MglB, yet paradoxically MglA and MglB are located at opposite poles at reversal initiation. Here we report the complete MglA/MglB structural cycle combined to GAP kinetics and in vivo motility assays, which uncovers that MglA is a three-state GTPase and suggests a molecular mechanism for concerted MglA/MglB relocalizations. We show that MglA has an atypical GTP-bound state (MglA-GTP*) that is refractory to MglB and is re-sensitized by a feedback mechanism operated by MglA-GDP. By identifying and mutating the pole-binding region of MglB, we then provide evidence that the MglA-GTP* state exists in vivo. These data support a model in which MglA-GDP acts as a soluble messenger to convert polar MglA-GTP* into a diffusible MglA-GTP species that re-localizes to the opposite pole during reversals.