Bauer Benedikt W, Shemesh Tom, Chen Yu, Rapoport Tom A
Howard Hughes Medical Institute, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Howard Hughes Medical Institute, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA; Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Cell. 2014 Jun 5;157(6):1416-1429. doi: 10.1016/j.cell.2014.03.063.
In bacteria, most secretory proteins are translocated across the plasma membrane by the interplay of the SecA ATPase and the SecY channel. How SecA moves a broad range of polypeptide substrates is only poorly understood. Here we show that SecA moves polypeptides through the SecY channel by a "push and slide" mechanism. In its ATP-bound state, SecA interacts through a two-helix finger with a subset of amino acids in a substrate, pushing them into the channel. A polypeptide can also passively slide back and forth when SecA is in the predominant ADP-bound state or when SecA encounters a poorly interacting amino acid in its ATP-bound state. SecA performs multiple rounds of ATP hydrolysis before dissociating from SecY. The proposed push and slide mechanism is supported by a mathematical model and explains how SecA allows translocation of a wide range of polypeptides. This mechanism may also apply to hexameric polypeptide-translocating ATPases.
在细菌中，大多数分泌蛋白通过SecA ATP酶和SecY通道的相互作用穿过质膜。SecA如何移动多种多肽底物目前了解甚少。在此我们表明，SecA通过“推和滑”机制使多肽穿过SecY通道。在其结合ATP的状态下，SecA通过一个双螺旋指与底物中的一部分氨基酸相互作用，将它们推入通道。当SecA处于主要的结合ADP的状态时，或者当SecA在其结合ATP的状态下遇到相互作用较弱的氨基酸时，多肽也可以被动地来回滑动。SecA在从SecY解离之前会进行多轮ATP水解。所提出的推和滑机制得到了一个数学模型的支持，并解释了SecA如何允许多种多肽的转运。这种机制也可能适用于六聚体多肽转运ATP酶。
