Proline Isomerization Regulates the Phase Behavior of Elastin-Like Polypeptides in Water

Responsiveness of polypeptides and polymers in aqueous solution plays an important role in biomedical applications and in designing advanced functional materials. Elastin-like polypeptides (ELPs) are a well-known class of synthetic intrinsically disordered proteins (IDPs), which exhibit a lower critical solution temperature (LCST) in pure water and in aqueous solutions. Here, we compare the influence of cis/trans proline isomerization on the phase behavior of single ELPs in pure water. Our results reveal that proline isomerization tunes the conformational behavior of ELPs while keeping the transition temperature unchanged. We find that the presence of the cis isomers facilitates compact structures by preventing peptide-water hydrogen bonding while promoting intramolecular interactions. In other words, the LCST transition of ELPs with all proline residues in the cis state occurs with almost no noticeable conformational change.