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Elucidating the structure of C. elegans TMC1 and TMC2


EMSL Project ID
51573

Abstract

Transmembrane channel-like (TMC) proteins are a unique family of channel-like proteins that are conserved from humans to C. elegans. Vertebrates express eight isoforms, two of which are essential for hearing and balance in vertebrates, TMC1 and TMC2. C. elegans express two TMC isoforms, TMC1 and TMC2, that share approximately 30% sequence homology with the human isoforms. In worms, TMC1/2 play important roles in chemosensation, reproduction, and development. Currently, there is no structural information available for TMC proteins, which limits our understanding of how they function. The objective of this project is to elucidate the structures of native TMC1 and TMC2 from C. elegans using single particle cryo-EM. We have developed methods for isolating TMC1 and TMC2 from transgenic worms that yields monodisperse protein in sufficient quantity to carry out single particle studies. The proposed studies will provide the first look at TMC1/2 architecture and illuminate its role in worm physiology and vertebrate mechanotransduction

Project Details

Start Date
N/A
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Eric Gouaux
Institution
Oregon Health & Science University

Team Members

Sarah Clark
Institution
Oregon Health & Science University

Heidi Owen
Institution
Oregon Health & Science University

Irina El Khoury
Institution
Environmental Molecular Sciences Laboratory

Trevor Moser
Institution
Environmental Molecular Sciences Laboratory