Kyndt John A, Fitch John C, Berry Robert E, Stewart Matt C, Whitley Kevin, Meyer Terry E, Walker F Ann, Cusanovich Michael A
Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
Biochim Biophys Acta. 2012 May;1817(5):811-8. doi: 10.1016/j.bbabio.2012.01.013. Epub 2012 Jan 28.
A triad of tyrosine residues (Y152-154) in the cytochrome c(1) subunit (C1) of the Rhodobacter capsulatus cytochrome bc(1) complex (BC1) is ideally positioned to interact with cytochrome c(2) (C2). Mutational analysis of these three tyrosines showed that, of the three, Y154 is the most important, since its mutation to alanine resulted in significantly reduced levels, destabilization, and inactivation of BC1. A second-site revertant of this mutant that regained photosynthetic capacity was found to have acquired two further mutations-A181T and A200V. The Y152Q mutation did not change the spectral or electrochemical properties of C1, and showed wild-type enzymatic C2 reduction rates, indicating that this mutation did not introduce major structural changes in C1 nor affect overall activity. Mutations Y153Q and Y153A, on the other hand, clearly affect the redox properties of C1 (e.g. by lowering the midpoint potential as much as 117 mV in Y153Q) and the activity by 90% and 50%, respectively. A more conservative Y153F mutant on the other hand, behaves similarly to wild-type. This underscores the importance of an aromatic residue at position Y153, presumably to maintain close packing with P184, which modeling indicates is likely to stabilize the sixth heme ligand conformation.
荚膜红细菌细胞色素bc1复合体(BC1)的细胞色素c1亚基(C1)中的一个由酪氨酸残基组成的三联体(Y152 - 154)处于与细胞色素c2(C2)相互作用的理想位置。对这三个酪氨酸的突变分析表明,其中Y154最为重要,因为将其突变为丙氨酸会导致BC1水平显著降低、稳定性下降以及失活。发现该突变体的一个恢复光合能力的第二位点回复突变体又获得了另外两个突变——A181T和A200V。Y152Q突变并未改变C1的光谱或电化学性质,并且显示出野生型的酶促C2还原速率,这表明该突变并未在C1中引入重大结构变化,也未影响整体活性。另一方面,Y153Q和Y153A突变明显影响C1的氧化还原性质(例如,Y153Q中中点电位降低多达117 mV),活性分别降低90%和50%。另一方面,一个更保守的Y153F突变体的行为与野生型相似。这强调了Y153位置芳香族残基的重要性,推测是为了与P184保持紧密堆积,模型显示这可能稳定第六个血红素配体构象。