The structural basis for an on–off switch controlling Gβγ-mediated inhibition of TRPM3 channels Article Swipe
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· 2020
· Open Access
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· DOI: https://doi.org/10.1073/pnas.2001177117
· OA: W3097075240
Significance µ-Opioid receptors, activated by endogenous peptides or opioid drugs such as morphine, dampen the activity of nociceptor cells that detect noxious stimuli and thereby reduce pain. These receptors achieve this clinically important action by inhibitory signaling with Gβγ proteins to ion channels. Here we study how precisely Gβγ proteins inhibit one particular pain-related ion channel, TRPM3. Using TRPM3 splice variants, we identify a short stretch of amino acids required for the inhibitory action of Gβγ. We then characterize the interacting surfaces on both proteins by using X-ray crystallography. Our in-depth characterization of this protein–protein interaction can serve as a basis to facilitate the development of novel pain-reducing drugs impinging upon the specific interface between Gβγ and TRPM3.
