Design for Solubility May Reveal Induction of Amide Hydrogen/Deuterium Exchange by Protein Self-Association

Trainor, Kyle; Doyle, Colleen; Metcalfe‐Roach, Avril; Steckner, Julia; Lipovšek, Daša; Malakian, Heather; Langley, David R.; Krystek, Stanley R.; Meiering, Elizabeth M.

doi:10.1016/j.jmb.2021.167398

Cited by 2 publications

(2 citation statements)

References 54 publications

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“…So, in the absence of allosteric affects, β-trefoil proteins with desirable functionality but only moderate stability may gain kinetic and thermodynamic stability from the replacement of core residues with those of another β-trefoil or from de novo core repacking. While allostery between the surface and the core may modulate binding ( Giri Rao and Gosavi, 2015 ; Ben-David et al, 2019 ), a variety of scaffolds bind diverse ligands just via loops (e.g., antibodies ( Warszawski et al, 2019 ), adnectins/monobodies ( Ng et al, 2007 ; Trainor et al, 2022 ), and repeat proteins ( Hansen et al, 2017 )]. Such proteins are attractive targets for engineering increased kinetic stability through increased long-range core contacts.…”

Section: Discussionmentioning

confidence: 99%

Engineering the kinetic stability of a β-trefoil protein by tuning its topological complexity

Anderson

Jayanthi²,

Gosavi³

et al. 2023

Front. Mol. Biosci.

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Kinetic stability, defined as the rate of protein unfolding, is central to determining the functional lifetime of proteins, both in nature and in wide-ranging medical and biotechnological applications. Further, high kinetic stability is generally correlated with high resistance against chemical and thermal denaturation, as well as proteolytic degradation. Despite its significance, specific mechanisms governing kinetic stability remain largely unknown, and few studies address the rational design of kinetic stability. Here, we describe a method for designing protein kinetic stability that uses protein long-range order, absolute contact order, and simulated free energy barriers of unfolding to quantitatively analyze and predict unfolding kinetics. We analyze two β-trefoil proteins: hisactophilin, a quasi-three-fold symmetric natural protein with moderate stability, and ThreeFoil, a designed three-fold symmetric protein with extremely high kinetic stability. The quantitative analysis identifies marked differences in long-range interactions across the protein hydrophobic cores that partially account for the differences in kinetic stability. Swapping the core interactions of ThreeFoil into hisactophilin increases kinetic stability with close agreement between predicted and experimentally measured unfolding rates. These results demonstrate the predictive power of readily applied measures of protein topology for altering kinetic stability and recommend core engineering as a tractable target for rationally designing kinetic stability that may be widely applicable.

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Section: Discussionmentioning

confidence: 99%

Engineering the kinetic stability of a β-trefoil protein by tuning its topological complexity

Anderson

Jayanthi²,

Gosavi³

et al. 2023

Front. Mol. Biosci.

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“…The solubility of proteins in aqueous solutions depends mainly on its conformation, while unfolding or misfolding structures of proteins is more likely to form aggregates (Trainor, et al, 2022). Casein is essentially a disordered protein with an unfolded conformation (Ginger & Grigor, 1999).…”

Section: Solubilitymentioning

confidence: 99%

Effect of hydrolysis and succinylation on the stability of dual-modified rennet casein and membrane separated casein emulsions under different environments

Hou

et al. 2022

Preprint

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Casein is a common ingredient and can be used to improve the stability of dairy products. However, the poor solubility and emulsification properties of casein limit its further application. Therefore, modification of casein to improve its application properties is important. In this study, hydrolysis and succinylation were used to modify the casein separated with different methods (rennet casein (RC) and membrane separated casein (MC)). And Turbiscan stability index (TSI), salt ion (Na+) stability, freeze-thaw stability and storage stability of emulsions prepared by RC and MC were investigated. The results showed that succinylation modified protein structure and improved the stability of oil-in-water emulsions prepared by succinylated casein and succinylated casein hydrolysates. The TSI of succinylated rennet casein (RC-SA) and succinylation of membrane separated casein hydrolysates (MC-CHs-SA) stabilized emulsions showed a better stability. Protein succinylation could prevent adsorption and aggregation between droplets, improving the Na+ stability and storage stability of the emulsion. Succinylated casein had the best emulsification activity and emulsion stability. And the solubility of succinylated casein hydrolysates was significantly improved compared with succinylated casein. Emulsions prepared with succinylated RC hydrolysates had the smallest particle size and a more uniform particle size distribution compared with other samples. Succinylated MC hydrolyzates showed the best freeze-thaw stability. Therefore, hydrolysis could reduce the molecular weight of casein and significantly improved the solubility of succinylated casein, and succinylation could modify the protein structure and significantly improved the emulsion stability. Overall, hydrolysis and succinylation can be applied to modify casein to effectively improve the application properties in emulsion system.

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Design for Solubility May Reveal Induction of Amide Hydrogen/Deuterium Exchange by Protein Self-Association

Cited by 2 publications

References 54 publications

Engineering the kinetic stability of a β-trefoil protein by tuning its topological complexity

Engineering the kinetic stability of a β-trefoil protein by tuning its topological complexity

Effect of hydrolysis and succinylation on the stability of dual-modified rennet casein and membrane separated casein emulsions under different environments

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