Fig. 5: Mechanism of cluster transport by Atm1.
From: Structures of Atm1 provide insight into [2Fe-2S] cluster export from mitochondria
We propose the inward-open configuration represents the resting state of eukaryotic Atm1 proteins, in which the protein exposes a highly electropositive cleft to the inside of the mitochondrial matrix, as detected in the CtAtm1inw-opn (and E603QCtAtm1inw-opn) structure. This state permits negatively charged glutathione-bound [2Fe-2S] clusters (red star) to associate in the vicinity of the cleft, as observed in our CtAtm1inw-open/cluster structure. Cargo and likely nucleotide binding to the positively charged cavity in the transmembrane domain and the nucleotide-binding domain, respectively, trigger conformational changes that result in reorganization of the F396 inner gate, partial occlusion (as in the CtAtm1inw-opn-occl structure) and then complete occlusion (as in the CtAtm1occl/ATP structure), with local chemistry of the cargo-binding pocket that is distinct to prokaryotic Atm1 proteins. We anticipate the [2Fe-2S] cluster or (an) intermediate(s) thereof is enclosed in the occluded state. Release to the intracellular side is likely coupled to further conformational adaptation, straightening of TM6 to permit passage across the inner gate, and opening the transport pathway. Once the cargo is liberated from the protein, ATP hydrolysis takes place, permitting a new transport cycle.
