Structural Biology Unit, Center for Cooperative Research in Biosciences bioGUNE, 48160 Derio, Spain.
Structure. 2010 Oct 13;18(10):1300-10. doi: 10.1016/j.str.2010.07.008.
Pyruvate carboxylase (PC) is a conserved multifunctional enzyme linked to important metabolic diseases. PC homotetramer is arranged in two layers with two opposing monomers per layer. Cryo-EM explores the conformational variability of PC in the presence of different substrates. The results demonstrate that the biotin-carboxyl carrier protein (BCCP) domain localizes near the biotin carboxylase (BC) domain of its own monomer and travels to the carboxyltransferase (CT) domain of the opposite monomer. All density maps show noticeable conformational differences between layers, mainly for the BCCP and BC domains. This asymmetry may be indicative of a coordination mechanism where monomers from different layers catalyze the BC and CT reactions consecutively. A conformational change of the PC tetramerization (PT) domain suggests a new functional role in communication. A long-range communication pathway between subunits in different layers, via interacting PT-PT and BC-BC domains, may be responsible for the cooperativity of PC from Staphylococcus aureus.
丙酮酸羧化酶 (PC) 是一种保守的多功能酶,与重要的代谢疾病有关。PC 四聚体排列成两层,每层有两个相对的单体。低温电镜探索了不同底物存在下 PC 的构象可变性。结果表明,生物素羧基载体蛋白 (BCCP) 结构域定位于其自身单体的生物素羧化酶 (BC) 结构域附近,并迁移到对面单体的羧基转移酶 (CT) 结构域。所有密度图都显示出层之间明显的构象差异,主要是在 BCCP 和 BC 结构域。这种不对称性可能表明一种协调机制,其中来自不同层的单体连续催化 BC 和 CT 反应。PC 四聚化 (PT) 结构域的构象变化表明其在通讯中具有新的功能作用。通过相互作用的 PT-PT 和 BC-BC 结构域,不同层之间亚基之间的长程通讯途径可能负责金黄色葡萄球菌 PC 的协同作用。