An ‘unprecedented look’ into the protein behind hypertension, epilepsy and other conditions

Washington University engineer will look into potential treatment candidates Read More

From the WashU Newsroom

The seemingly unrelated conditions of hypertension, epilepsy and overactive bladder may be linked by electrical activity in a protein long studied by a biomedical engineer at Washington University in St. Louis.

After new technology recently revealed the structure of the protein, the lab of Jianmin Cui, professor of biomedical engineering in the School of Engineering & Applied Science, will collaborate with two others to take an unprecedented look into its molecular mechanisms potentially leading to the development of new drugs for these and other conditions.

Cui has received a four-year, $2.9 million grant from the National Institutes of Health to study the BK (big potassium) channel proteins in collaboration with labs from the University of Missouri-Columbia and the University of Massachusetts. The labs will each play a role in identifying new compounds that could go into the drug development pipeline.

Cells have ion channels across the cell membrane, which are pathways that conduct electrical currents into or out of the cell and open in response to physical signals, such as voltage, or chemical signals, such as calcium ions. But these channels typically allow only one type of ion to pass through, for example, the BK channel only allows potassium to pass through.

Recently, another lab used a new, Nobel-Prize-winning method called cryo-electron microscopy that allowed them to see the structure of the BK channel, which has given Cui’s lab a fresh look at the channel’s mechanisms. While researchers already knew the channel has three different domains — the voltage-sensing domain, the cytosolic domain and the pore domain— they do not know how sensors in other domains open the gate in the pore domain. Cui’s lab seeks to find that pathway.

“In BK channel, the question is how would calcium binding in the cytosolic domain open the pore in the transmembrane pore domain,” Cui said. “We have the structural information, but the structure itself cannot answer the question of how the two domains will interact to propagate and transfer the movements in calcium binding that causes the cytosolic domain to open.”

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Posted on May 14, 2018
Posted in: Neurogenetics & Transcriptomics, News Authors: