Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Structure. 2021 Jan 7;29(1):43-49.e3. doi: 10.1016/j.str.2020.08.011. Epub 2020 Sep 15.
The Ni-Fe-S-containing A-cluster of acetyl-coenzyme A (CoA) synthase (ACS) assembles acetyl-CoA from carbon monoxide (CO), a methyl group (CH), and CoA. To accomplish this feat, ACS must bind CoA and interact with two other proteins that contribute the CO and CH, respectively: CO dehydrogenase (CODH) and corrinoid Fe-S protein (CFeSP). Previous structural data show that, in the model acetogen Moorella thermoacetica, domain 1 of ACS binds to CODH such that a 70-Å-long internal channel is created that allows CO to travel from CODH to the A-cluster. The A-cluster is largely buried and is inaccessible to CFeSP for methylation. Here we use electron microscopy to capture multiple snapshots of ACS that reveal previously uncharacterized domain motion, forming extended and hyperextended structural states. In these structural states, the A-cluster is accessible for methylation by CFeSP.
含 Ni-Fe-S 的乙酰辅酶 A (CoA) 合酶 (ACS) 的 A 簇将一氧化碳 (CO)、一个甲基 (CH) 和 CoA 组装成乙酰辅酶 A。为了完成这一壮举，ACS 必须结合 CoA 并与另外两个分别贡献 CO 和 CH 的蛋白质相互作用：一氧化碳脱氢酶 (CODH) 和钴胺素 Fe-S 蛋白 (CFeSP)。以前的结构数据表明，在模型产乙酸菌 Moorella thermoacetica 中，ACS 的结构域 1 与 CODH 结合，从而形成一条 70 Å 长的内部通道，允许 CO 从 CODH 转移到 A 簇。A 簇大部分被掩埋，无法与 CFeSP 进行甲基化。在这里，我们使用电子显微镜捕获 ACS 的多个快照，揭示了以前未表征的结构域运动，形成了扩展和超扩展的结构状态。在这些结构状态下，A 簇可被 CFeSP 进行甲基化。
