YALE (US)—Scientists have established a novel way to peer inside the hidden universe of cellular proteins, particularly those in cellular membranes—the molecular machinery of the human body. The work offers the first close-up look at a potassium ion channel that, when defective, can cause high blood pressure or epilepsy.
The Yale University team was able to visualize the so-called “BK” channel protein by using single-particle reconstruction. In this technique, individual protein molecules are imaged in an electron microscope, and information from thousands of images is combined to produce a three-dimensional map of the protein structure. This was the first time this reconstruction technique was extended to proteins embedded in membranes.
The researchers were able to see the BK channel protein’s voltage sensors, the calcium-sensing domains, and other aspects of this critical cellular component.
“The technique opens up a new way to study the many important molecular machines of cellular membranes,” says Fred Sigworth, a professor in Yale’s Department of Cellular and Molecular Physiology. “These machines include pumps, transporters, and receptors as well as ion channels like the one visualized here.”
Although the first map did not have high resolution, Sigworth and his coauthor Liguo Wang say they are optimistic that better 3-D visuals will be obtained in the future. Furthermore, this technique will now allow the proteins to be caught in the act as they respond to cellular signals and transport their molecular cargoes across membranes.
The research appears August 30 in Nature’s Advance Online Publication.
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