Abstract
Mechanically activated ion channels underlie touch, hearing, shear-stress sensing, and response to turgor pressure. OSCA/TMEM63s are a newly-identified family of eukaryotic mechanically activated ion channels opened by membrane tension. The structural underpinnings of OSCA/TMEM63 function are not explored. Here, we elucidate high resolution cryo-electron microscopy structures of OSCA1.2, revealing a dimeric architecture containing eleven transmembrane helices per subunit and surprising topological similarities to TMEM16 proteins. We locate the ion permeation pathway within each subunit by demonstrating that a conserved acidic residue is a determinant of channel conductance. Molecular dynamics simulations reveal membrane interactions, suggesting the role of lipids in OSCA1.2 gating. These results lay a foundation to decipher how the structural organization of OSCA/TMEM63 is suited for their roles as MA ion channels.
Highlights
Mechanosensation allows organisms to detect and respond to external and internal mechanical forces (Haswell et al, 2011)
Reported as putative ion channels sensitive to osmolality (Hou et al, 2014; Yuan et al, 2014; Zhao et al, 2016), a companion paper characterizes OSCA/TMEM63 family members as a novel family of mechanically activated (MA) ion channels conserved across eukaryotes (Murthy et al, 2018)
We purified Arabidopsis thaliana OSCA1.2 expressed in HEK293F cells and determined cryo-EM reconstructions in lipidic nanodiscs and Lauryl Maltose Neopentyl Glycol (LMNG) detergent micelle with cholesteryl hemisuccinate (CHS) at 3.1 and 3.5 Aresolution, respectively
Summary
Mechanosensation allows organisms to detect and respond to external and internal mechanical forces (Haswell et al, 2011). Mechanical stimuli such as touch, gravity, and osmotic pressure are sensed by mechanically activated (MA) ion channels (Haswell et al, 2011; Ranade et al, 2015). Plants with mutant OSCA1 have impaired osmotic stress signaling (Yuan et al, 2014), implying that OSCAs function as sensors of osmotic-stress induced mechanical force in vivo. To facilitate a mechanistic understanding of how OSCAs sense force in plants, and to shed light on a newly identified family of eukaryotic MA ion channels, we conducted cryo-EM studies of OSCA1.2
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