The structure of the SufBC2D-SufE complex reveals the mechanism of sulfur transfer in bacterial Fe-S cluster assembly.

Abstract

Iron-sulfur clusters are essential cofactors assembled in bacteria by the Suf pathway through a series of transient protein-protein interactions that transfer sulfur from L-cysteine to a scaffold complex. While early steps in persulfide transfer are well characterized, the mechanism of sulfur delivery to the SufBC2D scaffold has remained unresolved. Here, we report the first structure of the SufBC2D-SufE complex, capturing the final step in persulfide transfer in the Suf pathway. The structure reveals coordinated conformational changes in both SufB and SufE that expose the otherwise buried C254 acceptor site and position the SufE C51 loop beneath the SufB-SufD axis. Biochemical analysis of SufB variants demonstrates that substitutions in the globally conserved 220s {beta}-strand enhance SufE binding affinity and persulfide transfer rates, consistent with stabilization of a locally rearranged, transfer-competent conformation. Together, these results support a model in which conformational gating regulates persulfide transfer, providing a mechanism for controlling access to reactive sulfur intermediates.