[초청강연] Structure of the mechanosensory TMC-1 complex from C. elegans

Hanbin Jeong

Title
Structure of the mechanosensory TMC-1 complex from C. elegans

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.