Abstract
Co-translational folding (CTF) is a fundamental molecular process that ensures efficient protein biosynthesis, minimising the wasteful or hazardous formation of misfolded states. However, the complexity of this process makes it extremely challenging to characterise CTF pathways with high structural or temporal resolution. In this project we will combine the Christodoulou group’s world-leading expertise in the preparation and characterisation of translationally-arrested ribosome–nascent chain complexes using solution-state NMR spectroscopy, with simultaneous single-molecule force spectroscopy, to obtain unprecedented parallel structural and mechanistic insight into pathways of co-translational folding and misfolding.
References
[1] Cassaignau et al. (2016) Nat Methods 11, 1492-1507
[2] Cabrita et al. (2016) Nat Struct Mol Biol 23, 278-285
[3] Waudby et al. (2017) bioRxiv
[4] Kaiser et al. (2011) Science 334, 1723-1727
[5] Goldman et al. (2015) Science 348, 457-460
[6] Endoh et al. (2012) Anal Chem 84, 857-861