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

Yani Zhao,Kurt Kremer

doi:10.1021/acs.jpcb.1c04779

Yani Zhao, Kurt Kremer

Open Access

https://doi.org/10.1021/acs.jpcb.1c04779

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Abstract

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.

Highlights

Stimulus-triggered polypeptides are involved in a wide range of biological processes
Our results show that proline isomerization plays an important role in tuning the conformational behavior of Elastin-like polypeptides (ELPs) in water while keeping Tl unchanged
Our study reveals that the conformational behavior of ELPs and other proline-rich peptides can be regulated by proline isomerization while keeping their transition temperature unchanged

Summary

Introduction

Stimulus-triggered polypeptides are involved in a wide range of biological processes. Synthetic polymers that exhibit phase transitions have broad applications ranging from biomedical applications[5−9] to polymer materials design.[10−15] the microscopic understanding of the phase behavior of stimuli responsive polymers is crucial for the optimized future applications.[14,16]. Elastin-like polypeptides (ELPs)[16,17] are synthetic peptidelike polymers with pentapeptide repeat sequences Val-Pro-GlyXaa-Gly (VPGXG), where the guest residue Xaa can be any amino acid except proline. They typically exhibit a lower critical solution temperature (LCST) phase behavior in aqueous solution, with an expanded-to-collapsed conformational transition. The transition temperature Tl of ELPs is tunable and depends on the peptide sequence, the chain length,[18] and a number of external stimuli, such as changes in pH,[19] ion concentration,[20] and pressure.[21]

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