Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/160365
Title: Liquid-liquid phase separation of short histidine- and tyrosine-rich peptides: sequence specificity and molecular topology
Authors: Lim, Jessica
Kumar, Akshita
Low, Kimberly Jia Yi
Verma, Chandra Shekhar
Mu, Yuguang
Miserez, Ali
Pervushin, Konstantin
Keywords: Engineering::Chemical engineering
Issue Date: 2021
Source: Lim, J., Kumar, A., Low, K. J. Y., Verma, C. S., Mu, Y., Miserez, A. & Pervushin, K. (2021). Liquid-liquid phase separation of short histidine- and tyrosine-rich peptides: sequence specificity and molecular topology. Journal of Physical Chemistry B, 125(25), 6776-6790. https://dx.doi.org/10.1021/acs.jpcb.0c11476
Project: MOE 2019-T3-1-012 
Journal: Journal of Physical Chemistry B 
Abstract: The increasing realization of the prevalence of liquid-liquid phase separation (LLPS) across multiple length scales of biological constructs, from intracellular membraneless organelles to extracellular load-bearing tissues, has raised intriguing questions about intermolecular interactions regulating LLPS at the atomic level. Squid-beak derived histidine (His)- and tyrosine (Tyr)-rich peptides (HBpeps) have recently emerged as suitable short model peptides to precisely assess the roles of peptide motifs and single residues on the phase behavior and material properties of microdroplets obtained by LLPS. In this study, by systematically introducing single mutations in an HBpep, we have identified specific sticker residues that attract peptide chains together. We find that His and Tyr residues located near the sequence termini drive phase separation, forming interaction nodes that stabilize microdroplets. Combining quantum chemistry simulations with NMR studies, we predict atomic-level bond geometries and uncover inter-residue supramolecular interactions governing LLPS. These results are subsequently used to propose possible topological arrangements of the peptide chains, which upon expansion can help explain the three-dimensional network of microdroplets. The stability of the proposed topologies carried out through all-atom molecular dynamics simulations predicts chain topologies that are more likely to stabilize the microdroplets. Overall, this study provides useful guidelines for the de novo design of peptide coacervates with tunable phase behavior and material properties. In addition, the analysis of nanoscale topologies may pave the way to understand how client molecules can be trapped within microdroplets, with direct implications for the encapsulation and controlled release of therapeutics for drug delivery applications.
URI: https://hdl.handle.net/10356/160365
ISSN: 1520-6106
DOI: 10.1021/acs.jpcb.0c11476
Schools: School of Biological Sciences 
School of Materials Science and Engineering 
Organisations: Bioinformatics Institute, A*STAR
National University of Singapore
Research Centres: Biological & Biomimetic Material Laboratory @ NTU 
Center for Sustainable Materials
Rights: © 2021 American Chemical Society. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
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