biostudies-literatureDieter EMBasic Energy SciencesNational Institute of General Medical SciencesNIGMS NIH HHS2318-2333https://www.ebi.ac.uk/biostudies/studies/S-EPMC12375889biostudies-literatureUnknown599(16)Methanogenic archaea are particularly rich in iron-sulfur proteins, yet their roles remain largely enigmatic. Here, we characterized a Methanococcus voltae (Mvo) protein from the domain of unknown function (DUF) 2193 family, a group of proteins present primarily in archaea and characterized by a conserved cysteine-rich C-terminal motif. MvoDUF2193 was heterologously expressed and characterized by a range of spectroscopic and analytical methods. The results demonstrate that MvoDUF2193 binds a single [4Fe-4S] cluster per subunit and that cluster occupancy regulates the transition from an apo tetramer to a [4Fe-4S] monomeric form. We hypothesize that MvoDUF2193 serves a regulatory role in the cell, mediated by [Fe-S] cluster binding and changes in oligomeric state.FEBS lettersArchaeal protein containing domain of unknown function 2193 undergoes oligomeric reconfiguration upon iron-sulfur cluster binding.PMC12375889R01GM125924DE-SC0020246DE‐SC0020246Xiong JDieter EMBothner BTokmina-Lukaszewska MGuo YLarson JBroderick WEGreen JBroderick JBfalseArchaeal protein containing domain of unknown function 2193 undergoes oligomeric reconfiguration upon iron-sulfur cluster binding.Methanogenic archaea are particularly rich in iron-sulfur proteins, yet their roles remain largely enigmatic. Here, we characterized a Methanococcus voltae (Mvo) protein from the domain of unknown function (DUF) 2193 family, a group of proteins present primarily in archaea and characterized by a conserved cysteine-rich C-terminal motif. MvoDUF2193 was heterologously expressed and characterized by a range of spectroscopic and analytical methods. The results demonstrate that MvoDUF2193 binds a single [4Fe-4S] cluster per subunit and that cluster occupancy regulates the transition from an apo tetramer to a [4Fe-4S] monomeric form. We hypothesize that MvoDUF2193 serves a regulatory role in the cell, mediated by [Fe-S] cluster binding and changes in oligomeric state.2025-01-01T00:00:00Z2025 Aug2026-05-08T10:53:33.605Z2026-05-02T03:07:21.913ZS-EPMC123758894071599610.1002/1873-3468.70120