Structural basis of sulfide production in dissimilatory sulfur metabolism
TL;DR
High-resolution cryo-EM structures of DsrMKJOP from Archaeoglobus fulgidus are presented, alone, with menadiol and with the sulfur-carrying substrate DsrC-trisulfide, complemented by physiological and biochemical studies to clarify how SRM control the reactivity of sulfur to selectively achieve sulfide production.
Abstract
The membrane-bound DsrMK(JOP) complex is central to dissimilatory sulfur metabolism, including in sulfate-reducing microbes (SRM), a group that plays important roles in shaping planetary and human health. Despite this global importance, the mechanism of sulfide production and its links to energy conservation remain unclear. Here, we present high-resolution cryo-EM structures of DsrMKJOP from Archaeoglobus fulgidus, alone, with menadiol and with the sulfur-carrying substrate DsrC-trisulfide, complemented by physiological and biochemical studies. The results clarify how SRM control the reactivity of sulfur to selectively achieve sulfide production. While DsrC-trisulfide is highly stable in isolation, interaction with the DsrK subunit facilitates its hydrolytic activation, triggering a conformational change. This brings a perthiosulfenate sulfur intermediate into the catalytic pocket of DsrK for reduction at a single non-cubane [4Fe-4S] cluster, likely supported by a conserved non-ligating cysteine. DsrM harbors a structural quinone-binding site, but seems not to catalyze menaquinol oxidation, although this likely occurs in DsrMK complexes from different sulfur-metabolizing organisms. In DsrMKJOP, trisulfide reduction by DsrK is linked to quinol oxidation at DsrP, releasing protons to the periplasm to generate a proton-motive force.