Karamanou Spyridoula, Gouridis Giorgos, Papanikou Efrosyni, Sianidis Giorgos, Gelis Ioannis, Keramisanou Dimitra, Vrontou Eleftheria, Kalodimos Charalampos G, Economou Anastassios
Institute of Molecular Biology and Biotechnology, Foundation of Research and Technology-Hellas, Crete, Greece.
EMBO J. 2007 Jun 20;26(12):2904-14. doi: 10.1038/sj.emboj.7601721. Epub 2007 May 24.
The cornerstone of the functionality of almost all motor proteins is the regulation of their activity by binding interactions with their respective substrates. In most cases, the underlying mechanism of this regulation remains unknown. Here, we reveal a novel mechanism used by secretory preproteins to control the catalytic cycle of the helicase 'DEAD' motor of SecA, the preprotein translocase ATPase. The central feature of this mechanism is a highly conserved salt-bridge, Gate1, that controls the opening/closure of the nucleotide cleft. Gate1 regulates the propagation of binding signal generated at the Preprotein Binding Domain to the nucleotide cleft, thus allowing the physical coupling of preprotein binding and release to the ATPase cycle. This relay mechanism is at play only after SecA has been previously 'primed' by binding to SecYEG, the transmembrane protein-conducting channel. The Gate1-controlled relay mechanism is essential for protein translocase catalysis and may be common in helicase motors.
几乎所有运动蛋白功能的基石是通过与各自底物的结合相互作用来调节其活性。在大多数情况下，这种调节的潜在机制仍然未知。在这里，我们揭示了分泌前体蛋白用于控制SecA（前体蛋白转位酶ATP酶）的解旋酶“DEAD”运动催化循环的一种新机制。该机制的核心特征是一个高度保守的盐桥，即Gate1，它控制核苷酸裂口的打开/关闭。Gate1调节在前体蛋白结合结构域产生的结合信号向核苷酸裂口的传播，从而使前体蛋白的结合和释放与ATP酶循环进行物理偶联。这种中继机制仅在SecA先前通过与跨膜蛋白传导通道SecYEG结合而被“启动”后才起作用。由Gate1控制的中继机制对于蛋白转位酶催化至关重要，并且可能在解旋酶运动中很常见。
