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Structure determination of the HgcAB complex using metagenome sequence data: insights into microbial mercury methylation.


ABSTRACT: 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 HgII, methylmercury, or both. These findings refine our understanding of the mechanism of Hg methylation and expand the known repertoire of corrinoid methyltransferases in nature.

SUBMITTER: Cooper CJ 

PROVIDER: S-EPMC7305189 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Structure determination of the HgcAB complex using metagenome sequence data: insights into microbial mercury methylation.

Cooper Connor J CJ   Zheng Kaiyuan K   Rush Katherine W KW   Johs Alexander A   Sanders Brian C BC   Pavlopoulos Georgios A GA   Kyrpides Nikos C NC   Podar Mircea M   Ovchinnikov Sergey S   Ragsdale Stephen W SW   Parks Jerry M JM  

Communications biology 20200619 1


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 Esch  ...[more]

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