The cytoplasmic ATPase SecA and the membrane-embedded SecYEG channel assemble to form the functional Sec translocase. How this interaction primes and catalytically activates the translocase remains unclear. We now show that priming exploits a sophisticated nexus of intrinsic dynamics in SecA. Using atomistic simulations, single molecule FRET and hydrogen/deuterium exchange mass spectrometry we reveal multiple distributed dynamic islands that cross-talk with domain and quaternary motions. These dynamic elements are highly conserved and essential for function. Central to the nexus is a slender Stem through which, motions in the helicase ATPase domain of SecA biases how the preprotein binding domain rotates between open-closed clamping states. Multi-tier dynamics are enabled by an H-bonded framework covering most of the SecA structure and allowing conformational alterations with minimal energy inputs. As a result, dimerization, the channel and nucleotides select pre-existing conformations, and alter local dynamics to restrict or promote catalytic activity and clamp motions. These events prime the translocase for high affinity reception of non-folded preprotein clients. Such dynamics nexuses are likely universal and essential in multi-liganded protein machines.

中文翻译：

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内在动力学联系是转位酶启动的基础

细胞质ATPase SecA和膜嵌入的SecYEG通道组装形成功能性Sec易位酶。这种相互作用如何引发和催化激活转位酶尚不清楚。现在，我们表明启动可以利用SecA中内在动力学的复杂关系。使用原子模拟，单分子FRET和氢/氘交换质谱，我们揭示了多个分散的动态岛，它们与畴和四元运动相互干扰。这些动态元素是高度保守的，对于功能至关重要。链接的中心是细长的茎，通过该茎，SecA的解旋酶ATPase域中的运动会偏置前蛋白结合域在开闭钳位状态之间的旋转方式。多层动力学通过覆盖大多数SecA结构的H键框架实现，并允许以最少的能量输入进行构象改变。结果，二聚化，通道和核苷酸选择预先存在的构象，并改变局部动力学以限制或促进催化活性和钳制运动。这些事件引发了转位酶对未折叠的前蛋白客户的高亲和力接收。这种动态联系在多配位蛋白机器中可能是普遍的和必不可少的。