Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
Department of Physics, Arizona State University, Tempe, Arizona, USA.
Nat Struct Mol Biol. 2016 Mar;23(3):248-55. doi: 10.1038/nsmb.3164. Epub 2016 Feb 1.
To fully understand the transport mechanism of Na(+)/H(+) exchangers, it is necessary to clearly establish the global rearrangements required to facilitate ion translocation. Currently, two different transport models have been proposed. Some reports have suggested that structural isomerization is achieved through large elevator-like rearrangements similar to those seen in the structurally unrelated sodium-coupled glutamate-transporter homolog GltPh. Others have proposed that only small domain movements are required for ion exchange, and a conventional rocking-bundle model has been proposed instead. Here, to resolve these differences, we report atomic-resolution structures of the same Na(+)/H(+) antiporter (NapA from Thermus thermophilus) in both outward- and inward-facing conformations. These data combined with cross-linking, molecular dynamics simulations and isothermal calorimetry suggest that Na(+)/H(+) antiporters provide alternating access to the ion-binding site by using elevator-like structural transitions.
为了充分理解 Na(+)/H(+) 交换器的转运机制，有必要明确促进离子转运所需的全局重排。目前已经提出了两种不同的转运模型。一些报告表明，结构异构化是通过类似于在结构上不相关的钠偶联谷氨酸转运体同源物 GltPh 中观察到的大型电梯样重排来实现的。其他人则认为，离子交换只需要小的结构域运动，因此提出了一种传统的摆动束模型。在这里，为了解决这些差异，我们报告了相同的 Na(+)/H(+) 反向转运蛋白（来自 Thermus thermophilus 的 NapA）在向外和向内构象中的原子分辨率结构。这些数据结合交联、分子动力学模拟和等温热力学表明，Na(+)/H(+) 反向转运蛋白通过使用类似于电梯的结构转变为离子结合位点提供交替的访问。
