Abstract
Mechanosensitive ion channels transduce physical force into electrochemical signaling that underlies an array of fundamental physiological processes, including hearing, touch, proprioception, osmoregulation, and morphogenesis. The mechanosensitive channels of small conductance (MscS) constitute a remarkably diverse superfamily of channels critical for management of osmotic pressure. Here, we present cryo-electron microscopy structures of a MscS homolog from Arabidopsis thaliana, MSL1, presumably in both the closed and open states. The heptameric MSL1 channel contains an unusual bowl-shaped transmembrane region, which is reminiscent of the evolutionarily and architecturally unrelated mechanosensitive Piezo channels. Upon channel opening, the curved transmembrane domain of MSL1 flattens and expands. Our structures, in combination with functional analyses, delineate a structural mechanism by which mechanosensitive channels open under increased membrane tension. Further, the shared structural feature between unrelated channels suggests the possibility of a unified mechanical gating mechanism stemming from membrane deformation induced by a non-planar transmembrane domain.
Highlights
Mechanosensitive ion channels transduce physical force into electrochemical signaling that underlies an array of fundamental physiological processes, including hearing, touch, proprioception, osmoregulation, and morphogenesis
Different gating models derived from electron paramagnetic resonance (EPR) spectroscopy, molecular dynamics (MD) simulations, and recent cryo-EM studies have been proposed[20,23,24,25,26], and these competing models are actively debated[9,20]
When heterologously expressed in giant E. coli spheroplasts, MSL1 displays stretch-activated gating in excised patches and channel properties similar to those of E. coli mechanosensitive channels of small conductance (MscS) (EcMscS)[28], which demonstrates that MSL1 forms a functional mechanosensitive channel
Summary
Mechanosensitive ion channels transduce physical force into electrochemical signaling that underlies an array of fundamental physiological processes, including hearing, touch, proprioception, osmoregulation, and morphogenesis. The presumed closed and open structures suggest that TM1 and TM2 constitute a peripheral membrane ‘tension sensor’, which is attached to the central pore-lining helix TM3a followed by the amphipathic TM3b running approximately parallel to the membrane[15,16,17,18] According to this model, rotation and tilting of TM1 and TM2 as a rigid body under elevated membrane tension, accompanied by displacement of channel-bound lipid molecules, pulls TM3a to open the hydrophobic pore gate[16,18]. With only limited homology in the pore-lining helix and the subsequent cytosolic portion, many acquire extra transmembrane helices as well as additional extramembrane domains[3] These added structural elements may give rise to rich channel properties[27], which have probably evolved to fulfill adapted functionalities in particular physiological settings. In combination with electrophysiology experiments, reveal a structural mechanism by which (at least some) mechanosensitive channels open in response to increased membrane tension
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