The MscS channel from Corynebacterium glutamicum uses a non-canonical gating mechanism

The function and gating mechanism of Escherichia coli mechanosensitive channel of small conductance ( Ec MscS) is well understood, but it is unknown whether MscS homologs in other bacteria function the same way. Here, we show that the MscS homolog from Corynebacterium glutamicum ( Cg MscS) opens at a much higher membrane tension than Ec MscS but has otherwise similar functional characteristics. Cg MscS is also structurally similar to Ec MscS but features an extended transmembrane (TM) helix 2 that forms salt bridges with the cytoplasmic cage. Compared to the closed conformation, the TM1-2 sensor paddles in the inactivated conformation are rotated but not tilted, and, unlike Ec MscS, there is no change in the associated pocket lipids, thus establishing a gating mechanism distinct from Ec MscS that is not based on the "lipids-move-first" model. Because the TM2 extension is conserved in Actinobacteria but not other bacterial phyla, our findings suggest that MscS homologs have lineage-specific gating mechanisms.