Promiscuous archaeal ATP synthase concurrently coupled to Na+ and H+ translocation
Promiscuous archaeal ATP synthase concurrently coupled to Na+ and H+ translocation
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DOI：
10.1073/pnas.1115796109
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发表时间：
2012-01-17
影响因子：
11.1
通讯作者：
Mueller, Volker
中科院分区：
文献类型：
--
作者：
Schlegel, Katharina;Leone, Vanessa;Mueller, Volker
ATP酶是所有活细胞中ATP的主要来源。为了催化ATP合成，这些膜相关复合物使用由离子沿浓度梯度的跨膜扩散提供动力的旋转机制。ATP酶被认为是由H+或Na+驱动的，反映了其膜结构域中的不同结构基序，以及宿主生物体的不同代谢。在这里，我们研究了产甲烷古菌Methanosarcina acetivorans使用ATP水解和离子转运倒置膜囊泡的测定，并实验证明，其ATP合成酶的旋转机制耦合到同时易位的H+和Na+在生理条件下跨膜。使用自由能分子模拟，我们解释了这一前所未有的观察的离子选择性的结合位点的膜转子，这似乎已经通过氨基酸取代，使ATP合成M。乙酸菌可以由产甲烷产生的H+和Na+梯度驱动。我们提出，这种滥交是一种分子机制的适应生活在热力学极限。
ATP synthases are the primary source of ATP in all living cells. To catalyze ATP synthesis, these membrane-associated complexes use a rotary mechanism powered by the transmembrane diffusion of ions down a concentration gradient. ATP synthases are assumed to be driven either by H+ or Na+, reflecting distinct structural motifs in their membrane domains, and distinct metabolisms of the host organisms. Here, we study the methanogenic archaeon Methanosarcina acetivorans using assays of ATP hydrolysis and ion transport in inverted membrane vesicles, and experimentally demonstrate that the rotary mechanism of its ATP synthase is coupled to the concurrent translocation of both H+ and Na+ across the membrane under physiological conditions. Using free-energy molecular simulations, we explain this unprecedented observation in terms of the ion selectivity of the binding sites in the membrane rotor, which appears to have been tuned via amino acid substitutions so that ATP synthesis in M. acetivorans can be driven by the H+ and Na+ gradients resulting from methanogenesis. We propose that this promiscuity is a molecular mechanism of adaptation to life at the thermodynamic limit.