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CryoEM Current Practices Webinar: Strategies and Highlights from the National CryoEM Centers
Structure of the mechanosensory TMC-1 complex from C. elegans

Speaker: Hanbin Jeong, Ph.D., Postdoctoral Fellow in Gouaux Laboratory
HHMI/Oregon Health and Science University

Abstract: The sense of hearing and balance begins with the mechanosensory transduction (MT) channel, which converts mechanical stimuli into electrochemical signals, and which is typically localized within hair cells of the mammalian inner ear. Despite decades of effort focused on discovering the molecular architecture and mechanism of the MT channel complex, the structure of the complex has remained unresolved. Here we report the single-particle cryo-EM structure of the native TMC-1 complex isolated from C. elegans. The overall architecture of the complex adopts 2-fold-rotation symmetry, in which TMC-1 forms a domain-swapped dimeric structure through its C-terminal transmembrane helix. The auxiliary subunit TMIE, present in two copies, resides on the periphery of the complex, close to the pore-forming transmembrane helices of TMC-1, and participating in lipid-mediated interactions throughout the interface with TMC-1. CALM-1, an orthologue of vertebrate Ca2+ binding protein CIB2, binds to the cytosolic face of TMC-1 via highly conserved residues. The entire complex structure resembles the shape of an ‘accordion’, whereby the single transmembrane helixes of TMIE function as the accordion handles. From thorough particle classification, we identified a subset of TMC-1 complexes bound with ARRD-6, an arrestin-like protein, via interactions with the CALM-1 subunit. Together with molecular dynamics simulations, we visualize the membrane-embedded TMC-1 complex and propose structure-based gating mechanisms for the MT channel.

Hosted jointly by NCCAT, PNCC, & S2C2

Jan 26, 2023 12:00 PM in Eastern Time (US and Canada)

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