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Study elucidates mechanism of lipid regulation of ion channels

In a recent study published in Nature Communications on November 17, 2022, Wayland Cheng, MD, PhD, and colleagues identified a mechanism for how lipids facilitate activation of pentameric ligand-gated ion channels.

In this study, titled “Open-channel structure of a pentameric ligand-gated ion channel reveals a mechanism of leaflet-specific phospholipid modulation,” Dr. Cheng’s team sought to understand how membrane lipids impact the function of pentameric ligand-gated ion channels—the family of receptors in the brain that are the principal targets of anesthetics.

High-resolution structure of a lipid-bound pentameric ligand-gated ion channel

The Cheng Lab solved the structure of a pentameric ligand-gated ion channel in an open-channel conformation using single particle cryo-electron microscopy. The structure shows how these ion channels activate, and how lipids facilitate activation through binding to a specific site.

“Understanding how these ion channels are regulated at a detailed molecular level is important for the design of new anesthetics or sedatives,” said Dr. Cheng. “Targeting this lipid binding site could be a means to develop new drugs specific for these ion channels.”

Dr. Cheng completed his MD and PhD degrees via the prestigious Medical Scientist Training Program (MSTP) at Washington University School of Medicine in St. Louis. He then joined the ACGME-approved Academic Scholars Advancement Program (ASAP), an accelerated program in the Department of Anesthesiology at WashU that integrates internship, residency, clinical fellowship, as well as almost two years of dedicated research time into a five-year period.

“The ASAP program truly served as a catalyst for my research career by providing me with early, protected research time to establish foundational research projects,” said Dr. Cheng. “Those projects enabled me to obtain a career-development grant (K08) and start my own laboratory.”

As a T32 research scholar, in the last two years of the ASAP, and subsequently as an IARS Mentored Training Research Grant recipient and NIH K08 scholar, Dr. Cheng was mentored by Dr. Alex Evers. In 2021, he was the recipient of the Frontiers in Anesthesia Research Award. Dr. Cheng is an Assistant Professor in the Division of Basic Science Research and his research focuses on the structure and function of neuronal ligand-gated ion channels.