- Ruan lab @ Thomas Jefferson University
TRPM5 is a specialized protein that is concentrated in the taste buds, where it helps relay messages to and from cells. It has long been of interest to researchers due to its roles in taste perception and blood sugar regulation. Now, a team led by scientists at Van Andel Institute has published the first-ever high-resolution images of TRPM5, which reveal two areas that may serve as targets for new medications. The structures also may aid in the development of low-calorie alternative sweeteners that mimic sugar. The findings were published in Nature Structural and Molecular Biology.
In this study, we 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 stroke and other brain injuries. These gates, called proton-activated chloride channels (PAC), nest within cell membranes and regulate the passage of small molecules called chloride ions into and out of cells. This allows cells to sense and respond to their environment. The structures also may aid in the development of drugs that alleviate diseases with tissue acidosis. The findings were published in Nature.
In this study, we have for the first time described the near-atomic level structure of a molecular pathway that plays critical roles in human development, blood pressure regulation, inflammation and cell death. In particular, the study elucidated the conformational changes in the PANX1 channel during normal conditions versus times when the cells are undergoing apoptosis, a process that recycles damaged and dead cells. These variations cause molecules and ions to be routed through different areas of the channel and determine whether a large pore is open or closed. The findings were published in the journal Nature.
