Article abstract


Nature Structural & Molecular Biology 14, 1141 - 1149 (2007)
Published online: 25 November 2007 | doi:10.1038/nsmb1341

Straightening and sequential buckling of the pore-lining helices define the gating cycle of MscS

Bradley Akitake1,2, Andriy Anishkin1,2, Naili Liu1 & Sergei Sukharev1


We describe a mechanism connecting the adaptive behavior of the bacterial mechanosensitive channel MscS to the flexibility of the pore-lining helix TM3. Simulated expansion of the channel structure revealed straightening of a characteristic kink near Gly113 in the open state; return to the closed state produced an alternative kink at Gly121. Patch-clamp experiments showed that higher helical propensity introduced by a G113A mutation prevented inactivation. A similar mutation, G121A, kinetically impeded both closure and inactivation. Duplicating the glycines at each of these sites to increase flexibility produced directly opposite effects. The severely toxic G113A G121A mutation resulted in channels that could not inactivate or close with the release of tension. These data suggest that the open MscS features straight TM3 helices, which act as collapsible 'struts'. Closure and desensitization rely on buckling at Gly121, whereas the crystal-like kink at Gly113 is a feature of the inactivated state.

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  1. Department of Biology, University of Maryland, Building 144, College Park, Maryland 20742, USA.
  2. These authors contributed equally to this work.

Correspondence to: Sergei Sukharev1 e-mail: sukharev@umd.edu



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