Successful protein folding and structure formation is essential for maintaining cellular homeostasis. Protein folding, however, competes directly with potentially devastating misfolding, which can lead to a range of human conformational diseases. Protein biosynthesis as it occurs on the ribosome is the first place where the emerging nascent polypeptide chain faces its first opportunity to either beginning to fold or misfold, co-translationally. This project aims to develop a novel toolkit by combining biochemistry and integrative structural biology to rescue protein misfolding as it occurs within the cell by exploiting the unique structural and dynamic features of newly synthesising polypeptide chains.
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Waudby CA et al. Systematic mapping of free energy landscapes of a growing filamin domain during biosynthesis. Proc Natl Acad Sci U S A. 2018;115(39):9744-9749. doi: 10.1073/pnas.1716252115
Plessa E*, Chu LP* et al, Cotranslational protein misfolding and aggregation can begin on the ribosome (Manuscript available upon request).