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The energy cost of polypeptide knot formation and its folding consequences.

ABSTRACT: Knots are natural topologies of chains. Yet, little is known about spontaneous knot formation in a polypeptide chain-an event that can potentially impair its folding-and about the effect of a knot on the stability and folding kinetics of a protein. Here we used optical tweezers to show that the free energy cost to form a trefoil knot in the denatured state of a polypeptide chain of 120 residues is 5.8?±?1?kcal?mol-1. Monte Carlo dynamics of random chains predict this value, indicating that the free energy cost of knot formation is of entropic origin. This cost is predicted to remain above 3?kcal?mol-1 for denatured proteins as large as 900 residues. Therefore, we conclude that naturally knotted proteins cannot attain their knot randomly in the unfolded state but must pay the cost of knotting through contacts along their folding landscape.

SUBMITTER: Bustamante A

PROVIDER: S-EPMC5691195 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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The energy cost of polypeptide knot formation and its folding consequences.

Bustamante Andrés A Sotelo-Campos Juan J Guerra Daniel G DG Floor Martin M Wilson Christian A M CAM Bustamante Carlos C Báez Mauricio M

Nature communications 20171117 1

Knots are natural topologies of chains. Yet, little is known about spontaneous knot formation in a polypeptide chain-an event that can potentially impair its folding-and about the effect of a knot on the stability and folding kinetics of a protein. Here we used optical tweezers to show that the free energy cost to form a trefoil knot in the denatured state of a polypeptide chain of 120 residues is 5.8 ± 1 kcal mol<sup>-1</sup>. Monte Carlo dynamics of random chains predict this value, indicating ...[more]

PMID: 29146980

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