“Tsinghua-IBP Joint Research Group for Structural Biology”, Tsinghua University, Beijing 100084,
○Fei Sun Xia Huo Yujia Zhai Aojin Wang Jianxing Xu Dan Su Mark Bartlam Zihe Rao
The mitochondrial respiratory Complex II or succinate:ubiquinone oxidoreductase (SQR) is an integral membrane protein complex in both the tricarboxylic acid cycle and aerobic respiration. The first crystal structure of Complex II from porcine heart was solved at 2.4 Å resolution and its complex structure with inhibitors 3-nitropropionate and 2-thenoyltrifluoroacetone (TTFA) was solved at 3.5 Å resolution. Complex II comprises of two hydrophilic proteins, flavoprotein (Fp) and iron-sulfur protein (Ip), and two trans-membrane proteins (CybL and CybS), as well as prosthetic groups required for electron transfer from succinate to ubiquinone. The structure correlates the protein environments around prosthetic groups with their unique midpoint redox potentials. Two ubiquinone binding sites are discussed and elucidated by TTFA binding. The Complex II structure provides a bona fide model for study of the mitochondrial respiratory system and human mitochondrial diseases related to mutations in this complex.