A paralog of Pcc1 is the fifth core subunit of the KEOPS tRNA-modifying complex in Archaea

In Archaea and Eukaryotes, the synthesis of a universal tRNA modification, N-6-threonyl-carbamoyl adenosine (t(6)A), is catalyzed by the KEOPS complex composed of Kae1, Bud32, Cgi121, and Pcc1. A fifth subunit, Gon7, is found only in Fungi and Metazoa. Here, we identify and characterize a fifth KEOPS subunit in Archaea. This protein, dubbed Pcc2, is a paralog of Pcc1 and is widely conserved in Archaea. Pcc1 and Pcc2 form a heterodimer in solution, and show modest sequence conservation but very high structural similarity. The five-subunit archaeal KEOPS does not form dimers but retains robust tRNA binding and t(6)A synthetic activity. Pcc2 can substitute for Pcc1 but the resulting KEOPS complex is inactive, suggesting a distinct function for the two paralogs. Comparative sequence and structure analyses point to a possible evolutionary link between archaeal Pcc2 and eukaryotic Gon7. Our work indicates that Pcc2 regulates the oligomeric state of the KEOPS complex, a feature that seems to be conserved from Archaea to Eukaryotes. Many eukaryotic and archaeal tRNAs carry a modified adenosine (t(6)A) that is synthesized by the KEOPS complex, which is composed of four subunits. A fifth subunit (Gon7) is found only in fungi and metazoa. Here the authors show that archaea also possess a fifth subunit, which is structurally and functionally similar to eukaryotic Gon7.

Automated summary

The synthesis of t(6)A, a universal tRNA modification, is catalyzed by the KEOPS complex in Archaea and Eukaryotes. A fifth subunit, Gon7, is found only in Fungi and Metazoa. In this study, a fifth KEOPS subunit, Pcc2, is identified in Archaea and it is structurally and functionally similar to eukaryotic Gon7. Pcc2 regulates the oligomeric state of the KEOPS complex, which is conserved from Archaea to Eukaryotes.