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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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Monte Carlo time evolution of the average quasi-chemical interaction energy between the -helix and the rest of the chain, in the knotted AOTCase and unknotted OTCase.The upper curve shows the same quantity for a mutant of the natively knotted protein in which all residues in the C-terminal -helix are replaced by hydrophilic residues.
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pcbi-1002504-g007: Monte Carlo time evolution of the average quasi-chemical interaction energy between the -helix and the rest of the chain, in the knotted AOTCase and unknotted OTCase.The upper curve shows the same quantity for a mutant of the natively knotted protein in which all residues in the C-terminal -helix are replaced by hydrophilic residues.

Mentions: The effect is quantitatively illustrated in Fig. 7, which portrays the average strength of the non-native interaction potential energy between the amino acids in the C-terminal -helix of the AOTCase or the OTCase and all the other residues in the chain. It is seen that the average non-native attraction is consistently stronger in the case of the knotted protein by about , which is a sizable amount considering that the average is taken over all sampled structures, irrespective of their compactness and knotted topology.


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 quasi-chemical interaction energy between the -helix and the rest of the chain, in the knotted AOTCase and unknotted OTCase.The upper curve shows the same quantity for a mutant of the natively knotted protein in which all residues in the C-terminal -helix are replaced by hydrophilic residues.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1002504-g007: Monte Carlo time evolution of the average quasi-chemical interaction energy between the -helix and the rest of the chain, in the knotted AOTCase and unknotted OTCase.The upper curve shows the same quantity for a mutant of the natively knotted protein in which all residues in the C-terminal -helix are replaced by hydrophilic residues.
Mentions: The effect is quantitatively illustrated in Fig. 7, which portrays the average strength of the non-native interaction potential energy between the amino acids in the C-terminal -helix of the AOTCase or the OTCase and all the other residues in the chain. It is seen that the average non-native attraction is consistently stronger in the case of the knotted protein by about , which is a sizable amount considering that the average is taken over all sampled structures, irrespective of their compactness and knotted topology.

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