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Inner-ear Protein Structure Defined
Using a combination of crystallization and physics-based simulations, researchers defined the structure of a protein, cadherin-23, that helps mediate our perception of sound. Their findings show the protein to be a rigid structure whose strength results from calcium ions binding within it. However, mutations that interfere with calcium-ion binding undermine the protein's firm structure and make it less resilient. This provides a possible explanation for certain forms of inherited deafness. After viewing the photo gallery, read an accompanying story to learn more.
Photos and images by Joshua Touster and David Corey.
Hair cells of the inner ear have bundles of cilia on their top surfaces. Each cilium is connected to its neighbor by a fine filament known as a tip link, boxed here. Sound waves cause tension to be placed on the tip links, initiating a cascade of events that enable our brains to discern footsteps or voices or music.
David Corey, an HMS professor of neurobiology and a Howard Hughes Medical Institute investigator, led the team that identified the structure of a protein that makes up the tip links. This research unravels the molecular basis for mechanisms that may lead to some inherited forms of deafness.
The protein is composed of 27-segments and is illustrated here as the drop portion of an earring. The protein is far stiffer than previously thought.
The team responsible for the discovery includes (from left) Rachelle Gaudet, an associate professor in Harvard University's Department of Molecular and Cellular Biology; David Corey, a professor of neurobiology at Harvard Medical School; Wilhelm Weihofen, a post-doctoral fellow in Gaudet's lab; and Marcos Sotomayor, a research fellow in Corey's lab.
The team used a novel combination of protein crystallization and virtual-reality-like simulations to determine the atomic structure of the protein and to show how that structure behaved under stressed circumstances.