Data from: Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels

Calcium and integrin-binding protein 2 (CIB2) and CIB3 bind to
transmembrane channel-like 1 (TMC1) and TMC2, the pore-forming subunits of
the inner-ear mechano-electrical transduction (MET) apparatus. Whether
these interactions are functionally relevant across mechanosensory organs
and vertebrate species is unclear. Here we show that both CIB2 and CIB3
can form heteromeric complexes with TMC1 and TMC2 and are integral for MET
function in mouse cochlea and vestibular end organs as well as in
zebrafish inner ear and lateral line. Our AlphaFold 2 models suggest that
vertebrate CIB proteins can simultaneously interact with at least two
cytoplasmic domains of TMC1 and TMC2 as validated using nuclear magnetic
resonance spectroscopy of TMC1 fragments interacting with CIB2 and CIB3.
Molecular dynamics simulations of TMC1/2 complexes with CIB2/3 predict
that TMCs are structurally stabilized by CIB proteins to form cation
channels. Overall, our work demonstrates that intact CIB2/3 and TMC1/2
complexes are integral to hair-cell MET function in vertebrate
mechanosensory epithelia.