Biology subjects

Tsui, C. C.

Publications and source records attributed to Tsui, C. C..

3 recordsLinked to original sources

bioRxiv2021

Structural Insights into the Venus flytrap Mechanosensitive Ion Channel Flycatcher1

Flycatcher1 (FLYC1), a MscS homolog, has recently been identified as a candidate mechanosensitive (MS) ion channel involved in Venus flytrap prey recognition. FLYC1 is larger and its sequence diverges from previously studied MscS homologs, suggesting it has unique structural features that contribute to its function. Here, we characterized FLYC1 by cryo-electron microscopy, molecular dynamics simulations, and electrophysiology. Akin to bacterial MscS and plant MSL1 channels, we find that FLYC1 central core includes side portals in the cytoplasmic cage that regulate ion conduction, by identifying critical residues that modulate channel conductance. Topologically unique cytoplasmic flanking regions can adopt up or down conformations, making the channel asymmetric. Disruption of an up conformation-specific interaction severely delays channel deactivation by 40-fold likely due to stabilization of the channel open state. Our results illustrate novel structural features and likely conformational transitions that regulate mechano-gating of FLYC1.

biochemistry↗

bioRxiv2019

Structures of the Otopetrin Proton Channels Otop1 and Otop3

Otopetrins (Otop1-Otop3) comprise one of only two known eukaryotic proton-selective channel families. Otop1 is required for formation of otoconia and is a candidate mammalian sour taste receptor. Here, we report cryo-EM structures of zebrafish Otop1 and chicken Otop3 in lipid nanodiscs. The structures reveal a dimeric architecture of Otopetrins with each subunit consisting of twelve transmembrane helices divided into structurally related N and C domains. Cholesterol-like molecules occupy various sites in Otop1 and Otop3 and occlude a cavernous central tunnel. Two hydrophilic vestibules, as well as the intrasubunit interface between N and C domains, form conduits for water entry into the membrane plane in molecular dynamics simulations, suggesting they each could provide pathways for proton conduction. We also demonstrate the functional relevance of a salt bridge in the C domain vestibule by mutagenesis. Our results provide a structural basis for understanding the function of the Otopetrin proton channel family.

biochemistry↗

bioRxiv2018

Cryo-EM structure of the mechanically activated ion channel OSCA1.2

Introduction Introduction Main Author Contributions Expression constructs Protein expression and... Cryo-EM sample preparation and... Cryo-EM image processing Model building and refinement Molecular dynamics simulations Generation of mutant, cell... Electrophysiology Methods Data availability References Methods References Mechanically activated (MA) ion channels underlie touch, hearing, shear-stress sensing, and response to turgor pressure1,2. Previously reported as putative ion channels sensitive to osmolality3-5, members of ...

biophysics↗