Avoidance of protein unfolding constrains protein stability in long-term evolution

Razban, Rostam M; Dasmeh, Pouria; Serohijos, Adrian W.R.; Shakhnovich, E. I.

doi:10.1016/j.bpj.2021.03.042

Cited by 8 publications

(7 citation statements)

References 91 publications

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“…A relation between co‐evolution of sequences and thermodynamic and kinetic folding stability has indeed been pinpointed for specific proteins [29] or entire proteomes. [30] …”

Section: Resultsmentioning

confidence: 99%

Design of a Protein with Improved Thermal Stability by an Evolution‐Based Generative Model

et al. 2022

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Efficient design of functional proteins with higher thermal stability remains challenging especially for highly diverse sequence variants. Considering the evolutionary pressure on protein folds, sequence design optimizing evolutionary fitness could help designing folds with higher stability. Using a generative evolution fitness model trained to capture variation patterns in natural sequences, we designed artificial sequences of a proteinaceous inhibitor of pectin methylesterase enzymes. These inhibitors have considerable industrial interest to avoid phase separation in fruit juice manufacturing or reduce methanol in distillates, averting chromatographic passages triggering unwanted aroma loss. Six out of seven designs with up to 30 % divergence to other inhibitor sequences are functional and two have improved thermal stability. This method can improve protein stability expanding functional protein sequence space, with traits valuable for industrial applications and scientific research.

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“…A relation between co‐evolution of sequences and thermodynamic and kinetic folding stability has indeed been pinpointed for specific proteins [29] or entire proteomes. [30] …”

Section: Resultsmentioning

confidence: 99%

Design of a Protein with Improved Thermal Stability by an Evolution‐Based Generative Model

et al. 2022

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show abstract

“…Other well-studied proteins include the essential bacterial dihydrofolate reductase (DHFR), which reduces dihydrofolic acid to tetrahydrofolic during folate biosynthesis, as well as mammalian superoxide dismutase 1 (SOD1), which reduces superoxides to hydrogen peroxides to destroy damaging free superoxide radicals. Mutations that affect the stability of these proteins’ secondary and tertiary structures also alter their foldability 46–48 . More generally, proteins in the proteomes of E. coli, C. elegans, S. cerevisiae, and human vary widely in their thermodynamic stability 49,50 , which correlates with protein foldability 32 .…”

Section: Bodymentioning

confidence: 99%

Rapid evolutionary change in trait correlations of a single protein

Dasmeh

Zheng

Wagner

2022

Preprint

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Many organismal traits are genetically determined and covary in evolving populations. The resulting trait correlations can either help or hinder evolvability, i.e., the ability to bring forth new and adaptive phenotypes. The evolution of evolvability requires that trait correlations themselves must be able to evolve, but we know little about this ability. To learn more about it, we here study one of the simplest evolvable systems, a gene encoding a single protein, and two traits of this protein, namely the ability to emit yellow and green light. We show that correlations between these two traits can evolve rapidly through both mutation and selection on short evolutionary time scales. In addition, we show that these correlations are driven by a protein's ability to fold, because single mutations that alter foldability can dramatically change trait correlations. Since foldability is important for most proteins and their traits, mutations affecting protein folding may alter trait correlations mediated by many other proteins. Thus, mutations that affect protein foldability may also help shape the correlations of complex traits that are affected by hundreds of proteins.

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“…Other well-studied proteins include the essential bacterial dihydrofolate reductase (DHFR), which reduces dihydrofolic acid to tetrahydrofolic during folate biosynthesis, as well as mammalian superoxide dismutase 1 (SOD1), which reduces superoxides to hydrogen peroxides to destroy damaging free superoxide radicals. Mutations that affect the stability of these proteins' secondary and tertiary structures also alter their foldability [46][47][48] . More generally, proteins in the proteomes of E. coli, C. elegans, S. cerevisiae, and human vary widely in their thermodynamic stability 49,50 , which correlates with protein foldability 32 .…”

Section: Bodymentioning

confidence: 99%

Rapid evolutionary change in trait correlations of a single protein

Dasmeh

Zheng

Wagner

2022

Preprint

Self Cite

View full text Add to dashboard Cite

Many organismal traits are genetically determined and covary in evolving populations. The resulting trait correlations can either help or hinder evolvability – the ability to bring forth new and adaptive phenotypes. The evolution of evolvability requires that trait correlations themselves must be able to evolve, but we know little about this ability. To learn more about it, we here study one of the simplest evolvable systems, a gene encoding a single protein, and two traits of this protein, namely the ability to emit yellow and green light. We show that correlations between these two traits can evolve rapidly through both mutation and selection on short evolutionary time scales. In addition, we show that these correlations are driven by a protein’s ability to fold, because single mutations that alter foldability can dramatically change trait correlations. Since foldability is important for most proteins and their traits, mutations affecting protein folding may alter trait correlations mediated by many other proteins. Thus, mutations that affect protein foldability may also help shape the correlations of complex traits that are affected by hundreds of proteins.

show abstract

Avoidance of protein unfolding constrains protein stability in long-term evolution

Cited by 8 publications

References 91 publications

Design of a Protein with Improved Thermal Stability by an Evolution‐Based Generative Model

Design of a Protein with Improved Thermal Stability by an Evolution‐Based Generative Model

Rapid evolutionary change in trait correlations of a single protein

Rapid evolutionary change in trait correlations of a single protein

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