Supported by extensive molecular dynamics simulations, we assembled the first half of the G protein activation pathway — a major step toward understanding how GPCRs translate drug binding into cellular signaling. (7/n)

Excited to share our latest @nature.com: How does naloxone (Narcan) stop an opioid overdose? We determined the first GDP-bound μ-opioid receptor–G protein structures and found naloxone traps a novel "latent” state, preventing GDP release and G protein activation.💊🧪 🧵👇 www.nature.com/articles/s41...

We took this to an extreme, and were able to reconstitute these complexes (wildtype KOR and G protein!) in vitro and were able to obtain cryoEM reconstructions up to 3 A resolution. Strikingly, we observed the receptor in an entirely unexpected conformation:

Excited to present our lab's new work on GPCR antagonism: Contrary to popular belief, we propose that inverse agonists can bind to and act via GPCR:G protein complexes. We show this at KOR, through cellular assays, radioligand binding and cryoEM studies. A thread. 💊 🧪 www.nature.com/articles/s41...

An opioid with a literal, light-sensitive 'on/off switch' to avoid fatal side effects? Look no further - Azomorphine-3 (AM3)! The most exciting study I've been part of, thus far. With the labs of Seva Katritch, Dirk Trauner @dirktrauner.bsky.social and Josh Levitz.
www.biorxiv.org/content/10.1...