Dynamics of Nitric Oxide Controlled by Protein Complex in Bacterial System
Dynamics of Nitric Oxide Controlled by Protein Complex in Bacterial System
复制标题
细菌系统中蛋白质复合物控制一氧化氮的动态
DOI：
10.1073/pnas.1621301114
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Yoshitsugu Shiro and Takehiko Tosha
中科院分区：
文献类型：
--
作者：
Erina Terasaka;Kenta Yamada;Po-Hung Wang;Kanta Hosokawa;Raika Yamagiwa;Kimi Matsumoto;Shoko Ishii;Takaharu Mori;Kiyoshi Yagi;Hitomi Sawai;Hiroyuki Arai;Hiroshi Sugimoto;Yuji Sugita;Yoshitsugu Shiro and Takehiko Tosha
一氧化氮（NO）在生物过程中发挥着多种重要作用，尽管它的细胞毒性，提出了一个问题，生物系统如何控制NO的行动，以尽量减少其细胞毒性。作为这样一个系统的一个很好的例子，我们发现了一种可能性，即NO生成亚硝酸盐还原酶（NiR）与NO分解膜整合的NO还原酶（NOR）形成复合物，以在厌氧硝酸盐呼吸（称为反硝化）中由NiR产生NO后立即有效地捕获NO。一个NiR功能性同源二聚体和两个NOR分子的复合物的3.2-ε分辨率结构提供了这些酶如何在细胞中相互作用的想法，而由于膜拓扑结构，该结构可能不反映细胞中的结构。随后的全原子分子动力学（MD）模拟的酶复合物模型在膜和结构导向诱变表明，一些interenzyme盐桥和库仑相互作用的NiR与膜可以稳定的复合物的一个NiR同型二聚体和一个NOR分子，并有助于快速NO分解细胞。NO在NiR：NOR膜复合物中扩散的MD轨迹表明，作为一种合理的NO转移机制，从NiR释放的NO迅速迁移到膜中，然后与NOR结合。这些结果有助于我们理解细胞毒性NO作用的细胞控制机制。
Nitric oxide (NO) plays diverse and significant roles in biological processes despite its cytotoxicity, raising the question of how biological systems control the action of NO to minimize its cytotoxicity in cells. As a great example of such a system, we found a possibility that NO-generating nitrite reductase (NiR) forms a complex with NO-decomposing membrane-integrated NO reductase (NOR) to efficiently capture NO immediately after its production by NiR in anaerobic nitrate respiration called denitrification. The 3.2-Å resolution structure of the complex of one NiR functional homodimer and two NOR molecules provides an idea of how these enzymes interact in cells, while the structure may not reflect the one in cells due to the membrane topology. Subsequent all-atom molecular dynamics (MD) simulations of the enzyme complex model in a membrane and structure-guided mutagenesis suggested that a few interenzyme salt bridges and coulombic interactions of NiR with the membrane could stabilize the complex of one NiR homodimer and one NOR molecule and contribute to rapid NO decomposition in cells. The MD trajectories of the NO diffusion in the NiR:NOR complex with the membrane showed that, as a plausible NO transfer mechanism, NO released from NiR rapidly migrates into the membrane, then binds to NOR. These results help us understand the mechanism of the cellular control of the action of cytotoxic NO.