PA02_02 - Charting and disrupting cotranslational folding

PA02_02

Charting and disrupting cotranslational folding

D. Balchin^1,*

¹Protein Biogenesis Laboratory, The Francis Crick Institute, London, United Kingdom

 

Abstract: Natural proteins often form intricate multidomain, oligomeric architectures. This presents a prima facie challenge to cellular homeostasis, as topologically complex proteins seldom refold efficiently in vitro. I will discuss new mechanisms by which the ribosome promotes the folding of difficult-to-fold proteins. Using structural proteomics and cryo-EM, we show that the ribosomes changes the pathway of protein folding and directs homo-oligomer assembly to avoid mis-assembly. I will also present our progress in discovering molecules which bind selectively to cotranslational folding intermediates, suggesting a new opportunity to intervene in protein biogenesis for therapeutic benefit.

Disclosure of Interest: None declared