Structure of the V. cholerae Na+-pumping NADH:quinone oxidoreductase
Structure of the V. cholerae Na+-pumping NADH:quinone oxidoreductase
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DOI：
10.1038/nature14003
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发表时间：
2014-12-04
期刊：
影响因子：
64.8
通讯作者：
Fritz, Guenter
中科院分区：
文献类型：
--
作者：
Steuber, Julia;Vohl, Georg;Fritz, Guenter
呼吸链中的NADH氧化与跨膜的离子移位偶联以建立电化学梯度。钠转运型NADH：醌氧化还原酶（Na+-NQR）是一种广泛存在于病原菌中的膜蛋白复合物，由NqrA、B、C、D、E和F六个亚基组成。据我们所知，到目前为止还没有关于Na+-NQR复合物的结构信息。在这里，我们提出了在3.5埃分辨率的Na+-NQR复合物的晶体结构。辅因子在复合物的细胞质侧和周质侧的排列，以及在膜嵌入部分中间的迄今未知的铁中心，揭示了从NADH氧化细胞质NqrF亚基穿过膜到细胞质NqrC，并返回到位于细胞质中的NqrA上的qui no还原位点的电子转移途径。钠离子通道定位于亚基Nqr 13中，其代表Na+-NQR的最大膜亚基，并且在结构上与尿素和氨转运蛋白相关。的结构的基础上，我们提出了一种机制的氧化还原驱动的Na+易位的氧化还原状态的变化的黄素单核苷酸辅酶在NqrB触发Na+的运输通过所观察到的通道。
NADH oxidation in the respiratory chain is coupled to ion translocation across the membrane to build up an electrochemical gradient. The sodium -translocattng NADH:quinone oxidoreductase (Na+-NQR), amembrane protein complex widespread among pathogenic bacteria' consists of six subunits, NqrA, B, C, D, E and F. our knowledge, no structural information on the Na+-NQR complex has been available until now. Here we present the crystal structure of the Na+-NQR complex at 3.5 angstrom resolution. The arrangement of cofactors both at the cytoplasmic and the periplastnic side of the complex, together with a hitherto unknown iron centre in the midst of the membrane-embedded part, reveals an electron transfer pathway from the NADH- oxidizing cytoplasmic NqrF subunit across the membrane to the petiplasmic NqrC, and back to the qui none reduction site on NqrA located in the cytoplasm. A soditun channel was localized in subunit Nqr13, which represents the largest membrane subunit of the Na+-NQR and is structurally related to urea and ammonia transporters. On the basis of the structure we propose a mechanism of redox-driven Na+ translocation where the change in redox state of the flavin mononucleotide cofactor in NqrB triggers the transport of Na+ through the observed channel.