Cryo-EM data processing workflow.
<div><p>[Fe-S] clusters are ancient and ubiquitous protein co-factors, which contributed to the emergence of life in an anoxic planet. We have recently identified two minimal [Fe-S] biogenesis systems, MIS and SMS, inferred to be ancestral systems dating back to the Last Universal Common...
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2025
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| Summary: | <div><p>[Fe-S] clusters are ancient and ubiquitous protein co-factors, which contributed to the emergence of life in an anoxic planet. We have recently identified two minimal [Fe-S] biogenesis systems, MIS and SMS, inferred to be ancestral systems dating back to the Last Universal Common Ancestor and which gave rise to the well-studied modern Iron-Sulfur Cluster (ISC), Nitrogen Fixation (NIF), and Sulfur Mobilization (SUF) machineries. The present study focuses on the ancestor SMS from the hyperthermophilic archaeon <i>Methanocaldococcus jannaschii</i>. Biochemical and structural studies showed that SMS is made of a SmsC<sub>2</sub>B<sub>2</sub> heterotetratmer wherein the SmsC subunit hosts both ATP and [Fe-S] cluster binding sites. Binding of ATP and assembly of [Fe-S] were found to be mutually exclusive allowing for a regulatory coupling between binding of both substrates. Mutagenesis and in vitro transfer experiments revealed the key role of SmsC-contained Cys residues in cluster assembly. Strikingly, the SMS system rescued a non-viable <i>Escherichia coli</i> strain lacking endogenous ISC and SUF systems grown under anoxic conditions, in the presence of Na<sub>2</sub>S, indicating that sulfide is a source of sulfur for SMS. In addition, we predict that most archaea SmsC proteins hold a similar C-terminal [Fe-S] cluster assembly site. Taking into account those unique structural and functional features, we propose a mechanistic model describing how SmsC<sub>2</sub>B<sub>2</sub> assembles and distributes [4Fe-4S] clusters. Altogether this study established SMS as a new <i>bona fide</i> [Fe-S] biogenesis system that operated in anaerobic prokaryotes prior to evolve to SUF after the Great Oxydation Event.</p></div> |
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