Effect of additives on liquid droplets and aggregates of proteins

Abstract

This review briefly summarizes the effect of additives on the formation of liquid droplets and aggregates of proteins. Proteins have the property of forming liquid droplets and aggregates both in vivo and in vitro. The liquid droplets of proteins are mainly stabilized by electrostatic and cation-π interactions, whereas the amorphous aggregates are mainly stabilized by hydrophobic interactions. Crowders usually stabilize liquid droplets, whereas ions and hexandiols destabilize the droplets. Additives such as kosmotropes, sugars, osmolytes, and crowders promote the formation of amorphous aggregates, whereas additives such as arginine and chaotropes can prevent the formation of amorphous aggregates. Further, amyloid has a different mechanism for its formation from amorphous aggregates because it is primarily stabilized by a cross-β structure. These systematic analyses of additives will provide clues to controlling protein aggregations and will aid the true understanding of the transition of proteins from liquid droplets and aggregates.

Solubility Parameters of Amino Acids on Liquid–Liquid Phase Separation and Aggregation of Proteins

“…The phase separation of proteins is also valuable for industrial applications, such as the concentration and stabilization of antibodies and enzymes for use as drugs ( Kurinomaru et al, 2014 ; Izaki et al, 2015 ; Maruyama et al, 2015 ; Mimura et al, 2019 ). Furthermore, the phase separation of proteins from the dispersed and redispersed states can be controlled to some extent by small molecular additives ( Kurinomaru and Shiraki, 2017 ; Shiraki et al, 2020 ).…”

Transcription Regulators and Membraneless Organelles Challenges to Investigate Them

“…During transcription initiation, there is a low level of short RNAs that stimulate condensate formation. RNA molecules promote condensate formation through electrostatic interactions with proteins [ 108 ]. During transcription elongation, a high level of longer RNAs appear, so the negative charges are much higher than the positive charges, which causes the repulsion between the charges and condensate dissolution [ 107 ].…”

“…An important chemical that enables LLPS investigation is 1,6-hexanediol. This compound is known to disrupt liquid-like condensates by interfering with hydrophobic interactions [ 108 ]. Sensitivity to 1,6-hexanediol and also 1,2-pentanediol or 1,2-hexanediol is the characteristic for MLOs, for which contribution of hydrophobic interactions is observed.…”

Relevance of Amorphous and Amyloid-Like Aggregates of the p53 Core Domain to Loss of its DNA-Binding Activity

“…Thus, we further attempt to describe a mechanism for suppressing p53 aggregation to maintain its function, because p53 is aggregation-prone even in the wild-type, and the p53 aggregates can propagate and inactivate healthy p53 molecules, which results in a dominant negative phenotype ( Iwashita et al, 2018 ; Shiraki et al, 2020 ).…”