Biological complexity: protein hearing controls (Introduction)

by David Turell , Wednesday, August 22, 2018, 23:25 (2285 days ago) @ David Turell

It takes a specific protein to handle hearing an d balance:

https://www.sciencedaily.com/releases/2018/08/180822130959.htm

"Scientists at Harvard Medical School say they have ended a 40-year-quest for the elusive identity of the sensor protein responsible for hearing and balance.

"The results of their research, reported Aug. 22 in Neuron, reveal that TMC1, a protein discovered in 2002, forms a sound- and motion-activated pore that allows the conversion of sound and head movement into nerve signals that travel to the brain -- a signaling cascade that enables hearing and balance.

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"'We believe our findings settle that issue for good and yield definitive proof that TMC1 is the critical molecular sensor that converts sound and motion into electrical signals the brain can understand," said co-senior author Jeffrey Holt, Harvard Medical School professor of otolaryngology and of neurology at Boston Children's Hospital. "It is, indeed, the gatekeeper of hearing."

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"In an initial set of experiments, the research team found that TMC1 proteins assemble in pairs to form sound-activated pores, or ion channels. Given that most ion-channel proteins form clusters of three to seven units, TMC1's minimalistic pairing was a surprise. It also offered a helpful clue into its structure.

"Next, to map out the molecular architecture of the TMC1 protein, the scientists turned to computer predictive modeling. Such models work by predicting the most probable arrangement of a protein's building blocks based on the configuration of a close relative with a known structure. The algorithm revealed that TMC1's closest relative with known structure was a protein known as TMEM16.

"Each protein's function is determined by its structure -- the specific sequence and arrangement of amino acids, the building blocks of proteins. TMEM16's amino acid arrangement yielded a possible amino acid model for TMC1. (my bold)

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"Substituting 17 amino acids -- one at a time -- the researchers gauged whether and how each single substitution altered the cells' ability to respond to sound and allow the flow of ions.

"Of the 17 amino acid substitutions, 11 altered the influx of ions, and five did so dramatically, reducing ion flow by up to 80 percent, compared with nonmodified cells. One particular substitution blocked calcium influx completely, a finding that confirmed the precise location of the pore that normally allows calcium and potassium influx to initiate signal transmission.

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"The ability to hear a sound and distinguish its meaning as a threat or a mere nuisance, for example, is crucial for biologic survival -- think hearing the sound of a bear approaching in the woods. But among many higher species, hearing is also important for social bonding and interaction -- think recognizing different voices or changes in voice patterns and intonation. The exquisitely complex ability to detect changes in intonation begins with the opening of a tiny molecular gate in TMC1.

"'We now know that TMC1 forms the pore that enables sound detection in animals ranging from fish to birds to humans," Corey said. "It is truly the protein that lets us hear.'"

Comment: Once again a specific protein fits the bill. Only design can achieve this result. Note my bold about the specificity of a protein's structural design and its action.