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DOE OSTI · 3029897

A minimal SufB 2 C 2 complex functions as a [4Fe-4S] cluster scaffold in methanogenic archaea

Zhao, Cuiping [Louisiana State Univ., Baton Rouge, LA (United States)]·Shao, Nana [Univ. of Georgia, Athens, GA (United States)] (ORCID:000000033565885X)·Bryer, Nicole [Louisiana State Univ., Baton Rouge, LA (United States)]·Chen, Haotian [Louisiana State Univ., Baton Rouge, LA (United States)]·Whitman, William B. [Univ. of Georgia, Athens, GA (United States)] (ORCID:0000000312290423)·Vinyard, David J. [Louisiana State Univ., Baton Rouge, LA (United States)]·Liu, Yuchen [Louisiana State Univ., Baton Rouge, LA (United States)] (ORCID:0000000308425882)
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Abstract

Iron-sulfur clusters are essential cofactors in all domains of life, yet their biogenesis in obligately anaerobic archaea remains poorly understood. Here, we characterized the minimal two-protein SUF system in methanogenic archaea, composed solely of SufB and SufC. Using Methanococcus maripaludis as a model, we demonstrate that the SUF proteins from its native host form a stable SufB 2 C 2 heterotetramer that binds a [4Fe-4S] cluster via three conserved cysteines in SufC. Mutations of conserved cysteine and histidine residues of SufB do not impair cluster binding. The complex interacts with the SAM-containing methanogenesis marker protein 10 (MmpX), suggesting direct Fe-S cluster transfer from SufB 2 C 2 to target proteins. Mutational analysis of Methanothermococcus thermolithotrophicus proteins confirmed that SufC is the primary cluster-binding component, while SufB enhances ATPase and cluster transfer activities. Evolutionary comparisons suggest that this two-protein SUF system represents an ancestral form of Fe-S cluster biogenesis.

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59 BASIC BIOLOGICAL SCIENCESMmpXSufBSufCiron-sulfur proteinmethanogen

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Zhao, Cuiping [Louisiana State Univ., Baton Rouge, LA (United States)], Shao, Nana [Univ. of Georgia, Athens, GA (United States)] (ORCID:000000033565885X), Bryer, Nicole [Louisiana State Univ., Baton Rouge, LA (United States)], Chen, Haotian [Louisiana State Univ., Baton Rouge, LA (United States)], Whitman, William B. [Univ. of Georgia, Athens, GA (United States)] (ORCID:0000000312290423), Vinyard, David J. [Louisiana State Univ., Baton Rouge, LA (United States)], Liu, Yuchen [Louisiana State Univ., Baton Rouge, LA (United States)] (ORCID:0000000308425882). 2025-11-04. A minimal SufB 2 C 2 complex functions as a [4Fe-4S] cluster scaffold in methanogenic archaea. https://doi.org/10.1128/spectrum.02134-25

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