The quasi-atomic “maps” reveal the structure for maintaining pH balance in cells

For the first time, scientists have visualized a new class of molecular gates that maintain pH balance within brain cells, a critical function that keeps cells alive and helps prevent strokes and other brain injuries.

These gates, called proton-activated chloride channels (PACs), nest inside cell membranes and regulate the passage of small molecules called chloride ions into and out of cells. This allows the cells to perceive and respond to their environment.

“Proton-activated chloride channels have only recently been described, but they are critical for cell survival, particularly in the brain,” said Wei Lü, Ph.D., assistant professor at the Van Andel Institute and co. -author of the study, which was published today in Nature. “Our new images, coupled with our findings on how these channels work, provide much-needed molecular patterns that will help answer longstanding questions in the field and provide new insights into how these channels can be therapeutically targeted in disease.” .

The images reveal a structure similar to a bridal bouquet, with parts that change configuration in response to the ambient pH. When the pH changes from alkaline to acidic, a key pH sensor moves from its “resting” position and is placed in an “acid pocket”, which signals that the door that allows ions to enter and exit the cell must be open. This specific mechanism has never been described before.

This study is a collaboration between the Van Andel Institute’s Lü Lab and a group led by Zhaozhu Qiu, Ph.D., assistant professor at Johns Hopkins University School of Medicine and corresponding co-author of the paper. The Johns Hopkins team first reported the discovery of the PAC in Science last year.

Resolving CAP structures is another important initial step towards an understanding that may one day impact human health.