Título: Cryo-electron microscopy: moving beyond X-ray crystallography for membrane receptors and drug discovery

Ponente: Javier García-Nafría (LMB/MRC, Cambridge, UK-University of Zaragoza)

Día y hora:  4 de octubre a las 13:00 h

Lugar: SALA DE CONFERENCIAS, EDIFICIO I+D+i, CAMPUS RIO EBRO

Resumen:

Cryo-electron microscopy (cryo-EM) has undergone major advances during the last years, with special impact in structural biology of membrane proteins. I will review the advances in cryo-EM technology that made the ¨resolution revolution¨ possible, and then show its application to understand G-protein coupled receptors (GPCRs). GPCRs are the largest family of membrane proteins in the human body and are a target for ~35% of the currently approved FDA drugs. GPCRs sense a variety of molecules and transduce the signal to the intracellular milieu by coupling to heterotrimeric G-proteins. We used cryo-EM to obtain high-resolution structural information on GPCR-G protein complexes, starting to tackle one of the major questions in the field – the GPCR-G protein selectivity code. I will then analyse the state-of-the-art in using cryo-EM for structure-based drug discovery of membrane proteins.

References:

1. Cryo-EM structure of the adenosine A_2A receptor coupled to an engineered heterotrimeric G protein. García-Nafría J.*, Lee Y.*, Bai X., Carpenter B. & Tate CG. 2018. Elife. May 4;7. pii: e35946.

2. Cryo-EM structure of the serotonin 5-HT1B receptor coupled to heterotrimeric Go. García-Nafría J., Nehme R., Edwards P., Tate CG. 2018. Nature 558 (7711). 620-62

3. Cryo-EM structures of GPCRs coupled to Gs, Gi and Go.  García-Nafría J. and Tate CG. Molecular and Cellular Endocrinology. 2019, In press.

4. Cryo-Electron Microscopy: Moving Beyond X-ray Crystal Structures for Drug receptors and Drug development. García-Nafría J. and Tate CG. 2019. Annual Reviews in Pharmacology and Toxicology. 2020. In press (2019 Jul 26. doi: 10.1146.)