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The role of non-native interactions in the folding of knotted proteins.

Skrbić T, Micheletti C, Faccioli P - PLoS Comput. Biol. (2012)

Bottom Line: In addition, two different sets of pairwise amino acid interactions are considered: one promoting exclusively native interactions, and the other additionally including non-native quasi-chemical and electrostatic interactions.With the additional non-native interactions, knotting propensity remains negligible for the natively-unknotted OTCase while for AOTCase it is much enhanced.Analysis of the trajectories suggests that the different entanglement of the two transcarbamylases follows from the tendency of the C-terminal to point away from (for OTCase) or approach and eventually thread (for AOTCase) other regions of partly-folded protein.

View Article: PubMed Central - PubMed

Affiliation: ECT*- European Centre for Theoretical Studies in Nuclear Physics and Related Areas, Villazzano (Trento), Italy.

ABSTRACT
Stochastic simulations of coarse-grained protein models are used to investigate the propensity to form knots in early stages of protein folding. The study is carried out comparatively for two homologous carbamoyltransferases, a natively-knotted N-acetylornithine carbamoyltransferase (AOTCase) and an unknotted ornithine carbamoyltransferase (OTCase). In addition, two different sets of pairwise amino acid interactions are considered: one promoting exclusively native interactions, and the other additionally including non-native quasi-chemical and electrostatic interactions. With the former model neither protein shows a propensity to form knots. With the additional non-native interactions, knotting propensity remains negligible for the natively-unknotted OTCase while for AOTCase it is much enhanced. Analysis of the trajectories suggests that the different entanglement of the two transcarbamylases follows from the tendency of the C-terminal to point away from (for OTCase) or approach and eventually thread (for AOTCase) other regions of partly-folded protein. The analysis of the OTCase/AOTCase pair clarifies that natively-knotted proteins can spontaneously knot during early folding stages and that non-native sequence-dependent interactions are important for promoting and disfavouring early knotting events.

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Related in: MedlinePlus

Monte Carlo time evolution of the average knotting probabilities and fraction of native contacts of the natively-knotted AOTCase (top panel) and of the unknotted OTCase (bottom panel).The thin black curve shows the average fraction of formed native contacts. The knotting probabilities observed for the purely native potential and for the added non-native interactions are shown with thick blue and red lines, respectively.
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pcbi-1002504-g004: Monte Carlo time evolution of the average knotting probabilities and fraction of native contacts of the natively-knotted AOTCase (top panel) and of the unknotted OTCase (bottom panel).The thin black curve shows the average fraction of formed native contacts. The knotting probabilities observed for the purely native potential and for the added non-native interactions are shown with thick blue and red lines, respectively.

Mentions: The knotting propensity of AOTCase, which is natively knotted, is illustrated in the upper panel of Fig. 4 which portrays the fraction of configurations that are properly or improperly knotted during a given time-window of the MC dynamics.


The role of non-native interactions in the folding of knotted proteins.

Skrbić T, Micheletti C, Faccioli P - PLoS Comput. Biol. (2012)

Monte Carlo time evolution of the average knotting probabilities and fraction of native contacts of the natively-knotted AOTCase (top panel) and of the unknotted OTCase (bottom panel).The thin black curve shows the average fraction of formed native contacts. The knotting probabilities observed for the purely native potential and for the added non-native interactions are shown with thick blue and red lines, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375218&req=5

pcbi-1002504-g004: Monte Carlo time evolution of the average knotting probabilities and fraction of native contacts of the natively-knotted AOTCase (top panel) and of the unknotted OTCase (bottom panel).The thin black curve shows the average fraction of formed native contacts. The knotting probabilities observed for the purely native potential and for the added non-native interactions are shown with thick blue and red lines, respectively.
Mentions: The knotting propensity of AOTCase, which is natively knotted, is illustrated in the upper panel of Fig. 4 which portrays the fraction of configurations that are properly or improperly knotted during a given time-window of the MC dynamics.

Bottom Line: In addition, two different sets of pairwise amino acid interactions are considered: one promoting exclusively native interactions, and the other additionally including non-native quasi-chemical and electrostatic interactions.With the additional non-native interactions, knotting propensity remains negligible for the natively-unknotted OTCase while for AOTCase it is much enhanced.Analysis of the trajectories suggests that the different entanglement of the two transcarbamylases follows from the tendency of the C-terminal to point away from (for OTCase) or approach and eventually thread (for AOTCase) other regions of partly-folded protein.

View Article: PubMed Central - PubMed

Affiliation: ECT*- European Centre for Theoretical Studies in Nuclear Physics and Related Areas, Villazzano (Trento), Italy.

ABSTRACT
Stochastic simulations of coarse-grained protein models are used to investigate the propensity to form knots in early stages of protein folding. The study is carried out comparatively for two homologous carbamoyltransferases, a natively-knotted N-acetylornithine carbamoyltransferase (AOTCase) and an unknotted ornithine carbamoyltransferase (OTCase). In addition, two different sets of pairwise amino acid interactions are considered: one promoting exclusively native interactions, and the other additionally including non-native quasi-chemical and electrostatic interactions. With the former model neither protein shows a propensity to form knots. With the additional non-native interactions, knotting propensity remains negligible for the natively-unknotted OTCase while for AOTCase it is much enhanced. Analysis of the trajectories suggests that the different entanglement of the two transcarbamylases follows from the tendency of the C-terminal to point away from (for OTCase) or approach and eventually thread (for AOTCase) other regions of partly-folded protein. The analysis of the OTCase/AOTCase pair clarifies that natively-knotted proteins can spontaneously knot during early folding stages and that non-native sequence-dependent interactions are important for promoting and disfavouring early knotting events.

Show MeSH
Related in: MedlinePlus