HOUSTON, Oct. 9 (Xinhua) -- Researchers in the U.S. Texas state used imaging techniques to reveal how proteins on the surface of nerve cells control gates that turn chemical signals into electrical signals.
According to a news release by the Rice University on Monday, the finding is a step forward in detailing mechanisms involved in neurological disease.
Researchers at the Rice University and the University of Teas Health Science Center at Houston (UTHealth) employed single-molecule FRET imaging techniques to establish a beachhead at the NMDA receptor gate that, when activated, allows ions to flow through the nerve cell's membrane.
FRET stands for Förster resonance energy transfer. It is a way to use the light emitted by two fluorescent-tagged molecules as a sensitive ruler for very small distances, such as the opening in the NMDA receptor channel. NMDA is a glutamate receptor and ion channel protein found in nerve cells.
Rice chemist Christy Landes, an expert in single-molecule FRET, and Vasanthi Jayaraman, a professor of biochemistry and molecular biology at UTHealth's McGovern Medical School, whose expertise is in NMDA receptor biochemistry, teamed to gather the first experimental evidence detailing the dynamics of how the receptors alter their shapes to control the sensitivity of the gate to chemical signals.
In an earlier study, the team analyzed the conformations of a smaller and simpler but related system, the C-clamp-like agonist binding domain of another receptor, AMPA. AMPA mediates fast signal transmission in the central nervous system.
The single-molecule FRET technique allowed the researchers to get the first snapshots of the AMPA protein's various clamp conformations at rest and also when bound to a range of target molecules by measuring the distance between two light-activated molecular tags.
The new study appears in Nature Chemical Biology. Drew Dolino, an alumnus of the University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, and graduate student Sudeshna Chatterjee of Rice are lead authors of the paper.
