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bioRxiv · 10.64898/2026.09.02.748947

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

Nakayama, Y.·Hiotis, G.·Walz, T.
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Abstract

The function and gating mechanism of Escherichia coli mechanosensitive channel of small conductance (EcMscS) 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 (CgMscS) opens at a much higher membrane tension than EcMscS but has otherwise similar functional characteristics. CgMscS is also structurally similar to EcMscS 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 EcMscS, there is no change in the associated pocket lipids, thus establishing a gating mechanism distinct from EcMscS 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.

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Nakayama, Y., Hiotis, G., Walz, T.. 2026-09-08. The MscS channel from Corynebacterium glutamicum uses a non-canonical gating mechanism. https://doi.org/10.64898/2026.09.02.748947

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