Yu C A, Xia D, Kim H, Deisenhofer J, Zhang L, Kachurin A M, Yu L
Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater 74078-3035, USA.
Biochim Biophys Acta. 1998 Jun 10;1365(1-2):151-8. doi: 10.1016/s0005-2728(98)00055-3.
The crystal structure of the cytochrome bc1 complex (ubiquinol-cytochrome c reductase) from bovine heart submitochondria was determined at 2.9 A resolution. The bc1 complex in crystal exists as a closely interacting dimer, suggesting that the dimer is a functional unit. Over half of the mass of the complex, including subunits core 1 and core 2, are on the matrix side of the membrane, while most of the cytochrome b subunit is located within the membrane. There are 13 transmembrane helices in each monomer, eight of them belonging to cytochrome b. Two large cavities are made of the transmembrane helices D, C, F and H in one monomer and helices D' and E' from the other monomer of cytochrome b, and the transmembrane helices of c1, iron-sulfur protein (ISP), and subunits 10 and 11. These cavities provide entrances for ubiquinone or inhibitor and connect the Qi pocket of one monomer and the Qo pocket of the other monomer. Ubiquinol made at the Qi site of one monomer can proceed to the nearby Qo site of the other monomer without having to leave the bc1 complex. The soluble parts of cytochrome c1 and ISP, including their redox prosthetic groups, are located on the cytoplasmic side of the membrane. The distances between the four redox centers in the complex have been determined, and the binding sites for several electron transfer inhibitors have been located. Structural analysis of the protein/inhibitor complexes revealed that the extramembrane domain of the Rieske iron-sulfur protein may undergo substantial movement during the catalytic cycle of the complex. The Rieske protein movement and the larger than expected distance between FeS and cytochrome c1 heme suggest that electron transfer reaction between FeS and cytochrome c1 may involve movements or conformational changes in the soluble domain of iron-sulfur protein. The inhibitory function of E-beta-methoxyacrylate-stilbene and myxothiazol may result from the increase of mobility in ISP, whereas the function of stigmatellin and 5-undecyl-6-hydroxy-4,7-dioxobenzothiazole may result from the immobilization of ISP.
牛心亚线粒体细胞色素bc1复合物（泛醌 - 细胞色素c还原酶）的晶体结构在2.9埃分辨率下被确定。晶体中的bc1复合物以紧密相互作用的二聚体形式存在，这表明二聚体是一个功能单元。复合物超过一半的质量，包括核心1和核心2亚基，位于膜的基质侧，而细胞色素b亚基的大部分位于膜内。每个单体中有13个跨膜螺旋，其中8个属于细胞色素b。两个大腔由细胞色素b的一个单体中的跨膜螺旋D、C、F和H以及另一个单体中的螺旋D'和E'，以及c1、铁硫蛋白（ISP）、10和11亚基的跨膜螺旋构成。这些腔为泛醌或抑制剂提供入口，并连接一个单体的Qi口袋和另一个单体的Qo口袋。在一个单体的Qi位点产生的泛醇可以在不离开bc1复合物的情况下进入另一个单体附近的Qo位点。细胞色素c1和ISP的可溶性部分，包括它们的氧化还原辅基，位于膜的胞质侧。复合物中四个氧化还原中心之间的距离已被确定，并且几种电子传递抑制剂的结合位点也已定位。蛋白质/抑制剂复合物的结构分析表明，在复合物的催化循环中，Rieske铁硫蛋白的膜外结构域可能会发生显著移动。Rieske蛋白的移动以及FeS与细胞色素c1血红素之间比预期更大的距离表明，FeS与细胞色素c1之间的电子传递反应可能涉及铁硫蛋白可溶性结构域的移动或构象变化。E-β-甲氧基丙烯酸 - 芪和粘噻唑的抑制功能可能源于ISP流动性的增加，而柱晶白霉素和5 - 十一烷基 - 6 - 羟基 - 4,7 - 二氧代苯并噻唑的功能可能源于ISP的固定化。
