New information may lead to treatments for hearing loss

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Researchers at Oregon Health & Science University (OSHU) have discovered 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 “TMC-1 complex structures illuminate mechanosensory transduction.”

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

“This is the last sensory system in which this fundamental molecular machinery has remained unknown,” explained lead author Eric Gouaux, PhD, senior scientist at OHSU Vollum Institute and researcher at the Howard Hughes Medical Institute. “The molecular machinery that performs this absolutely incredible process has not been solved for decades.”

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

The researchers revealed the structure by cryo-electron microscopy. Their findings could pave the way for the development of new treatments for hearing loss.

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

Hearing loss can be inherited through genetic mutations or it can result from damage, including prolonged exposure to loud noise. Either way, the OHSU researchers’ discovery allows scientists to visualize the complex for the first time.

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

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