Researchers at Oregon Health & Science University (OSHU) have uncovered for the first time and in near-atomic detail, the structure of the key part of the inner ear responsible for hearing.

Their findings are published in the journal Nature in an article titled, “Structures of the TMC-1 complex illuminate mechanosensory transduction.”

“The initial step in the sensory transduction pathway underpinning hearing and balance in mammals involves the conversion of force into the gating of a mechanosensory transduction channel,” wrote the researchers. “Despite the profound socioeconomic impacts of hearing disorders and the fundamental biological significance of understanding mechanosensory transduction, the composition, structure, and mechanism of the mechanosensory transduction complex have remained poorly characterized. Here we report the single-particle cryo-electron microscopy structure of the native transmembrane channel-like protein 1 (TMC-1) mechanosensory transduction complex isolated from Caenorhabditis elegans.”

“This is the last sensory system in which that fundamental molecular machinery has remained unknown,” explained senior author Eric Gouaux, PhD, senior scientist with the OHSU Vollum Institute and a Howard Hughes Medical Institute investigator. “The molecular machinery that carries out this absolutely amazing process has been unresolved for decades.”

The researchers made the discovery by teasing out the structure through years of painstaking research to isolate the process that enables the inner ear to convert vibrations into sound, known as the mechanosensory transduction complex.

The researchers revealed the structure through cryo-electron microscopy. Their findings may pave the way for developing new treatments for hearing impairments.

“It immediately suggests mechanisms by which one might be able to compensate for those deficits,” Gouaux said. “If a mutation gives rise to a defect in the transduction channel that causes hearing loss, it’s possible to design a molecule that fits into that space and rescues the defect. Or it may mean we can strengthen interactions that have been weakened.”

Hearing loss can be inherited through gene mutations or it can occur from damage, including sustained exposure to loud noise. In either case, OHSU researchers’ discovery allows scientists to visualize the complex for the first time.

“The auditory neuroscience field has been waiting for these results for decades, and now that they are right here—we are ecstatic,” said Peter Barr-Gillespie, PhD, an OHSU research scientist and national leader in hearing research. “The results from this paper immediately suggest new avenues of research, and so will invigorate the field for years to come.”

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