TMEM266 is a functional voltage sensor regulated by extracellular Zn2.

ELife
Ferenc PappKenton J Swartz

Abstract

Voltage-activated ion channels contain S1-S4 domains that sense membrane voltage and control opening of ion-selective pores, a mechanism that is crucial for electrical signaling. Related S1-S4 domains have been identified in voltage-sensitive phosphatases and voltage-activated proton channels, both of which lack associated pore domains. hTMEM266 is a protein of unknown function that is predicted to contain an S1-S4 domain, along with partially structured cytoplasmic termini. Here we show that hTMEM266 forms oligomers, undergoes both rapid (µs) and slow (ms) structural rearrangements in response to changes in voltage, and contains a Zn2+ binding site that can regulate the slow conformational transition. Our results demonstrate that the S1-S4 domain in hTMEM266 is a functional voltage sensor, motivating future studies to identify cellular processes that may be regulated by the protein. The ability of hTMEM266 to respond to voltage on the µs timescale may be advantageous for designing new genetically encoded voltage indicators.

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Citations

Aug 30, 2019·Proceedings of the National Academy of Sciences of the United States of America·Richard BanhThomas E DeCoursey
Feb 28, 2021·Communications Biology·Chang Zhao, Francesco Tombola

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Datasets Mentioned

BETA
BAA79939.1

Methods Mentioned

BETA
X-ray
Confocal microscopy
pulldown
pulldowns
Fluorescence
Light Imaging
ion exchange chromatography

Software Mentioned

BioNJ
Fiji
Phenix
Phyre2
MEGA
Image Lab
Clustal Omega
pCLAMP
BLAST
Arclight

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