What is the trigger mechanism for the reversal of electron flow in oxygen-tolerant [NiFe] hydrogenases?

The [NiFe] hydrogenases use an electron transfer relay of three FeS clusters - proximal, medial and distal to release the electrons from the principal reaction, H-2 -> 2H(+) + 2e(-), that occurs at the Ni-Fe catalytic site. This site is normally inactivated by O-2, but the subclass of O-2-tolerant [NiFe] hydrogenases are able to counter this inactivation through the agency of an unusual and unprecedented proximal cluster, with composition [Fe4S3(S-cys)(6)], that is able to transfer two electrons back to the Ni-Fe site and effect crucial reduction of O-2-derived species and thereby reactivate the Ni-Fe site. This proximal cluster gates both the direction and the number of electrons flowing through it, and can reverse the normal flow during O-2 attack. The unusual structures and redox potentials of the proximal cluster are known: a structural change in the proximal cluster causes changes in its electron-transfer potentials. Using protein structure analysis and density functional simulations, this paper identifies a closed protonic system comprising the proximal cluster, some contiguous residues, and a proton reservoir, and proposes that it is activated by O-2-induced conformational change at the Ni-Fe site. This change is linked to a key histidine residue which then causes protonation of the proximal cluster, and migration of this proton to a key mu(3)-S atom. The resulting SH group causes the required structural change at the proximal cluster, modifying its redox potentials, and leads to the reversed electron flow back to the Ni-Fe site. This cycle is reversible, and the protons involved are independent of those used or produced in reactions at the active site. Existing experimental support for this model is cited, and new testing experiments are suggested.