Dataset Information

How Quickly Do Proteins Fold and Unfold, and What Structural Parameters Correlate with These Values?

ABSTRACT: The correlations between the logarithm of the unfolding rate of 108 proteins and their structural parameters were calculated. We showed that there is a good correlation between the logarithm of folding and unfolding rates (0.79) and protein stability and unfolding rate (0.79). Thus, the faster the protein folds, the faster it unfolds. Folding and unfolding rates are higher for the proteins with two-state kinetics, in comparison with the proteins with multi-state kinetics. At the same time, two-state bacterial proteins folds and unfolds two orders of magnitude faster than two-state eukaryotic proteins, and multi-state bacterial proteins folds and unfolds slower than multi-state eukaryotic proteins. Despite the fact that the folding rates of thermophilic and mesophilic proteins are close, the unfolding rates of thermophilic proteins is about two orders of magnitude lower than for mesophilic proteins. The correlation between unfolding rate and stability of thermophilic proteins is high (0.90). We also found that the unfolding rate correlates with such structural parameters as: size of the protein, radius of the cross-section, logarithm of absolute contact order, and radius of gyration. This information will be useful for engineering and designing new proteins with desired properties.

SUBMITTER: Glyakina AV

PROVIDER: S-EPMC7072309 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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How Quickly Do Proteins Fold and Unfold, and What Structural Parameters Correlate with These Values?

Glyakina Anna V AV Galzitskaya Oxana V OV

Biomolecules 20200129 2

The correlations between the logarithm of the unfolding rate of 108 proteins and their structural parameters were calculated. We showed that there is a good correlation between the logarithm of folding and unfolding rates (0.79) and protein stability and unfolding rate (0.79). Thus, the faster the protein folds, the faster it unfolds. Folding and unfolding rates are higher for the proteins with two-state kinetics, in comparison with the proteins with multi-state kinetics. At the same time, two-s ...[more]

PMID: 32013136

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Project description:After the surprisingly low number of genes identified in the human genome, alternative splicing emerged as a major mechanism to generate protein diversity in higher eukaryotes. However, it is still not known if its prevalence along the genome evolution has contributed to the overall functional protein diversity or if it simply reflects splicing noise. The (??)8 barrel or TIM barrel is one of the most frequent, versatile, and ancient fold encountered among enzymes. Here, we analyze the structural modifications present in TIM barrel proteins from the human genome product of alternative splicing events. We found that 87% of all splicing events involved deletions; most of these events resulted in protein fragments that corresponded to the (??)2, (??)4, (??)5, (??)6, and (??)7 subdomains of TIM barrels. Because approximately 7% of all the splicing events involved internal ?-strand substitutions, we decided, based on the genomic data, to design ?-strand and ?-helix substitutions in a well-studied TIM barrel enzyme. The biochemical characterization of one of the chimeric variants suggests that some of the splice variants in the human genome with ?-strand substitutions may be evolving novel functions via either the oligomeric state or substrate specificity. We provide results of how the splice variants represent subdomains that correlate with the independently folding and evolving structural units previously reported. This work is the first to observe a link between the structural features of the barrel and a recurrent genetic mechanism. Our results suggest that it is reasonable to expect that a sizeable fraction of splice variants found in the human genome represent structurally viable functional proteins. Our data provide additional support for the hypothesis of the origin of the TIM barrel fold through the assembly of smaller subdomains. We suggest a model of how nature explores new proteins through alternative splicing as a mechanism to diversify the proteins encoded in the human genome.

Dataset Information

How Quickly Do Proteins Fold and Unfold, and What Structural Parameters Correlate with These Values?

Publications

How Quickly Do Proteins Fold and Unfold, and What Structural Parameters Correlate with These Values?

Similar Datasets

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