Protein kinetic stability

Sanchez-Ruiz, José M.

doi:10.1016/j.bpc.2010.02.004

Cited by 321 publications

(331 citation statements)

References 211 publications

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“…Generally speaking, such an increase in fitness is biophysically plausible because each of the subfunctionalized sequences may afford a higher kinetic stability [81] to one or the other functional structure than that provided by a bi-stable sequence [239]. However, divergence does not always have to be adaptive.…”

Section: Protein Divergence Driven By Gene Duplication and Mutationalmentioning

confidence: 99%

Biophysics of protein evolution and evolutionary protein biophysics

Sikosek

Chan

2014

J. R. Soc. Interface.

220

207

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The study of molecular evolution at the level of protein-coding genes often entails comparing large datasets of sequences to infer their evolutionary relationships. Despite the importance of a protein's structure and conformational dynamics to its function and thus its fitness, common phylogenetic methods embody minimal biophysical knowledge of proteins. To underscore the biophysical constraints on natural selection, we survey effects of protein mutations, highlighting the physical basis for marginal stability of natural globular proteins and how requirement for kinetic stability and avoidance of misfolding and misinteractions might have affected protein evolution. The biophysical underpinnings of these effects have been addressed by models with an explicit coarse-grained spatial representation of the polypeptide chain. Sequence-structure mappings based on such models are powerful conceptual tools that rationalize mutational robustness, evolvability, epistasis, promiscuous function performed by 'hidden' conformational states, resolution of adaptive conflicts and conformational switches in the evolution from one protein fold to another. Recently, protein biophysics has been applied to derive more accurate evolutionary accounts of sequence data. Methods have also been developed to exploit sequence-based evolutionary information to predict biophysical behaviours of proteins. The success of these approaches demonstrates a deep synergy between the fields of protein biophysics and protein evolution.

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Section: Protein Divergence Driven By Gene Duplication and Mutationalmentioning

confidence: 99%

Biophysics of protein evolution and evolutionary protein biophysics

Sikosek

Chan

2014

J. R. Soc. Interface.

220

207

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“…Whereas thermodynamic stability can be explained at the molecular level, there are no simple structural elements pinpointed to the improved kinetic stability of the enzyme so far. 37 Our efforts have not produced any clear evidence in this field as well.…”

Section: Protein Denaturation Studies Using CDmentioning

confidence: 93%

Biophysical characterization of mutants of Bacillus subtilis lipase evolved for thermostability: Factors contributing to increased activity retention

Augustyniak

Brzezinska

Pijning³

et al. 2012

Protein Science

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Previously, Lipase A from Bacillus subtilis was subjected to in vitro directed evolution using iterative saturation mutagenesis, with randomization sites chosen on the basis of the highest B-factors available from the crystal structure of the wild-type (WT) enzyme. This provided mutants that, unlike WT enzyme, retained a large part of their activity after heating above 65°C and cooling down. Here, we subjected the three best mutants along with the WT enzyme to biophysical and biochemical characterization. Combining thermal inactivation profiles, circular dichroism, X-ray structure analyses and NMR experiments revealed that mutations of surface amino acid residues counteract the tendency of Lipase A to undergo precipitation under thermal stress. Reduced precipitation of the unfolding intermediates rather than increased conformational stability of the evolved mutants seems to be responsible for the activity retention.

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“…This model is usually known as the Lumry-Eyring mechanism (Lumry and Eyring 1954;Sanchez-Ruiz 2010). According to the relative values of the kinetic coefficients, two main scenarios can be envisaged (Sanchez-Ruiz 1992).…”

Section: Kinetic Stability: the Two-state Irreversible Modelmentioning

confidence: 99%

“…Among these, differential scanning calorimetry (Galisteo and Sanchez-Ruiz 1993;Sedlák et al 2014) has provided the most valuable information on the energetics of the involved processes (for a good discussion, see Sanchez-Ruiz 1992, 2010. In addition, some new approaches, such as pulse proteolysis (Di Bartolo et al 2016;Schlebach et al 2011) and steric trapping (Jefferson et al 2013), are becoming promising tools to explore complementary aspects of protein kinetic stability.…”

Section: Kinetic Stability: the Two-state Irreversible Modelmentioning

confidence: 99%

Kinetic stability of membrane proteins

2017

Biophys Rev

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Although membrane proteins constitute an important class of biomolecules involved in key cellular processes, study of the thermodynamic and kinetic stability of their structures is far behind that of soluble proteins. It is known that many membrane proteins become unstable when removed by detergent extraction from the lipid environment. In addition, most of them undergo irreversible denaturation, even under mild experimental conditions. This process was found to be associated with partial unfolding of the polypeptide chain exposing hydrophobic regions to water, and it was proposed that the formation of kinetically trapped conformations could be involved. In this review, we will describe some of the efforts toward understanding the irreversible inactivation of membrane proteins. Furthermore, its modulation by phospholipids, ligands, and temperature will be herein discussed.

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Protein kinetic stability

Cited by 321 publications

References 211 publications

Biophysics of protein evolution and evolutionary protein biophysics

Biophysics of protein evolution and evolutionary protein biophysics

Biophysical characterization of mutants of Bacillus subtilis lipase evolved for thermostability: Factors contributing to increased activity retention

Kinetic stability of membrane proteins

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