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Rational design of phase separating peptides based on phase separating protein sequence of p53.
Kiyoto Kamagata1,2,3,4, Atsumi Hando5,6, Maulana Ariefai5,7
1Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Aoba-ku, Sendai, 980-8577, Japan. kiyoto.kamagata.e8@tohoku.ac.jp.
Scientific Reports
|April 6, 2023
Summary
Researchers developed a rational method for designing artificial phase-separating (PS) peptides. These peptides form liquid droplets and co-phase separate with target proteins, showing potential for microreactors and drug delivery.
Area of Science:
- Biochemistry
- Materials Science
- Biotechnology
Background:
- Artificial phase-separating (PS) peptides are valuable for applications like microreactors and drug delivery.
- Designing effective artificial PS peptides is challenging due to limited residue interactions and difficulty in targeting specific proteins.
Purpose of the Study:
- To propose a rational method for designing artificial PS peptides.
- To enable liquid droplet formation and co-phase separation with target PS proteins.
- To validate the method using the p53 protein model.
Main Methods:
- Developed a rational design strategy for artificial PS peptides based on target protein sequences.
- Synthesized five artificial peptides derived from the p53 protein.
- Utilized differential interference contrast and fluorescence microscopy to confirm PS properties.
- Employed single-molecule fluorescent tracking to analyze peptide and protein dynamics.
Main Results:
- Confirmed phase-separating properties of designed peptides.
- Observed rapid diffusion of designed peptides within their droplets.
- Demonstrated size-dependent uptake of p53 oligomers, with larger oligomers localized on the surface.
- Showed that designed peptide droplets recruit p53, suppressing gel-like aggregate formation.
Conclusions:
- The proposed rational method successfully designs artificial PS peptides with desired phase-separation behaviors.
- The designed peptides exhibit distinct dynamics and interaction profiles with target proteins.
- Artificial PS peptides can be engineered to control protein aggregation and facilitate targeted delivery.
