Protein folding and protein stabilization are essential for modern biotechnology and biochemistry. Molecular chaperones are found ubiquitously in vivo for protein folding and prevention of protein aggregation. However, fabrication of such complicated chaperone system in vitro remains challenging. In this study, we show that four-monomer random heteropolymers (RHPs) can modulate membrane protein folding during cell-free translation in a manner similar to molecular chaperones. Membrane proteins are prone to misfolding and aggregation in aqueous solution. Here, we observe improvements in folding of three model transmembrane proteins, Aquaporin Z (water channel,helices), PeoTso (proton transporter, helices) and OmpT (protease, barrel), when RHP are present in cell-free expression. The ability to aid in the proper folding of membrane proteins can be tailored by controlling the composition and segmental distribution of RHPs. Our results demonstrate that some RHP features, specifically the degree of hydrophobicity and statistical randomness, significantly impact the folding of a membrane protein. Present studies suggest that chaperone-like activity can be realized and tuned in a synthetic heterogeneous system lack of precise sequence control.

Chaperone-like heteropolymers mediate membrane protein folding during translation

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.