TY - JOUR
T1 - Structure determination of the HgcAB complex using metagenome sequence data
T2 - insights into microbial mercury methylation
AU - Cooper, Connor J.
AU - Zheng, Kaiyuan
AU - Rush, Katherine W.
AU - Johs, Alexander
AU - Sanders, Brian C.
AU - Pavlopoulos, Georgios A.
AU - Kyrpides, Nikos C.
AU - Podar, Mircea
AU - Ovchinnikov, Sergey
AU - Ragsdale, Stephen W.
AU - Parks, Jerry M.
N1 - Publisher Copyright:
© 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85086736962&partnerID=8YFLogxK
U2 - 10.1038/s42003-020-1047-5
DO - 10.1038/s42003-020-1047-5
M3 - Article
C2 - 32561885
AN - SCOPUS:85086736962
SN - 2399-3642
VL - 3
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 320
ER -