Bacteria and archaea possessing the hgcAB gene pair methylate inorganic mercury (Hg) to form highly toxic methylmercury. HgcA consists of a corrinoid binding domain and a transmembrane domain, and HgcB is a dicluster ferredoxin. However, their detailed structure and function have not been thoroughly characterized. We modeled the HgcAB complex by combining metagenome sequence data mining, coevolution analysis, and Rosetta structure calculations. In addition, we overexpressed HgcA and HgcB in Escherichia coli, confirmed spectroscopically that they bind cobalamin and [4Fe-4S] clusters, respectively, and incorporated these cofactors into the structural model. Surprisingly, the two domains of HgcA do not interact with each other, but HgcB forms extensive contacts with both domains. The model suggests that conserved cysteines in HgcB are involved in shuttling Hg^II, methylmercury, or both. These findings refine our understanding of the mechanism of Hg methylation and expand the known repertoire of corrinoid methyltransferases in nature.

具有hgcAB基因对的细菌和古细菌对甲基化无机汞（Hg）形成高毒性甲基汞。HgcA由类固醇结合结构域和跨膜结构域组成，而HgcB是双歧铁氧还蛋白。但是，它们的详细结构和功能尚未得到充分表征。我们通过结合元基因组序列数据挖掘，协同进化分析和Rosetta结构计算对HgcAB复合物进行建模。另外，我们在大肠杆菌中过表达HgcA和HgcB ，在光谱上证实它们分别结合钴胺素和[4Fe-4S]簇，并将这些辅因子结合到结构模型中。出乎意料的是，HgcA的两个域彼此不相互作用，但是HgcB与这两个域形成广泛的联系。该模型表明，HgcB中保守的半胱氨酸参与穿梭Hg ^II和/或甲基汞。这些发现完善了我们对汞甲基化机理的理解，并扩大了自然界中已知的类rinrinoid甲基转移酶库。