The ClpXP degradation machine consists of a hexameric AAA+ unfoldase (ClpX) and a pair of heptameric serine protease rings (ClpP) that unfold, translocate, and subsequently degrade client proteins. ClpXP is an important target for drug development against infectious diseases. Although structures are available for isolated ClpX and ClpP rings, it remains unknown how symmetry mismatched ClpX and ClpP work in tandem for processive substrate translocation into the ClpP proteolytic chamber. Here we present cryo-EM structures of the substrate-bound ClpXP complex from Neisseria meningitidis at 2.3 to 3.3 Å resolution. The structures allow development of a model in which the sequential hydrolysis of ATP is coupled to motions of ClpX loops that lead to directional substrate translocation and ClpX rotation relative to ClpP. Our data add to the growing body of evidence that AAA+ molecular machines generate translocating forces by a common mechanism.

中文翻译：

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连续旋转机制将ClpXP降解机械中的底物展开和蛋白水解耦合在一起

ClpXP降解机器由六聚体AAA +解折叠酶（ClpX）和一对七聚体丝氨酸蛋白酶环（ClpP）组成，这些环解折叠，转运并随后降解客户蛋白。ClpXP是开发抗传染病药物的重要目标。尽管结构可用于隔离的ClpX和ClpP环，但仍不知道对称错配的ClpX和ClpP如何协同工作以将底物进行处理性转运至ClpP蛋白水解室。在这里，我们介绍脑膜炎奈瑟氏球菌与底物结合的ClpXP复合物的冷冻-EM结构。分辨率为2.3至3.3Å。该结构允许开发一个模型，在该模型中，ATP的顺序水解与ClpX环的运动耦合，从而导致定向底物易位和ClpX相对于ClpP的旋转。我们的数据增加了越来越多的证据，即AAA +分子机器通过共同的机制产生移位力。