Abstract
Diverse aerobic bacteria use atmospheric H-2 as an energy source for growth and survival(1). This globally significant process regulates the composition of the atmosphere, enhances soil biodiversity and drives primary production in extreme environments(2,3). Atmospheric H-2 oxidation is attributed to uncharacterized members of the [NiFe] hydrogenase superfamily(4,5). However, it remains unresolved how these enzymes overcome the extraordinary catalytic challenge of oxidizing picomolar levels of H-2 amid ambient levels of the catalytic poison O-2 and how the derived electrons are transferred to the respiratory chain(1). Here we determined the cryo-electron microscopy structure of the Mycobacterium smegmatis hydrogenase Huc and investigated its mechanism. Huc is a highly efficient oxygen-insensitive enzyme that couples oxidation of atmospheric H-2 to the hydrogenation of the respiratory electron carrier menaquinone. Huc uses narrow hydrophobic gas channels to selectively bind atmospheric H-2 at the expense of O-2, and 3 [3Fe-4S] clusters modulate the properties of the enzyme so that atmospheric H-2 oxidation is energetically feasible. The Huc catalytic subunits form an octameric 833 kDa complex around a membrane-associated stalk, which transports and reduces menaquinone 94 angstrom from the membrane. These findings provide a mechanistic basis for the biogeochemically and ecologically important process of atmospheric H-2 oxidation, uncover a mode of energy coupling dependent on long-range quinone transport, and pave the way for the development of catalysts that oxidize H-2 in ambient air.