The energy cost of polypeptide knot formation and its folding consequences.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29146980.
- Also identified by DOI 10.1038/s41467-017-01691-1 and PMC identifier 5691195.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-1</sup>. 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<sup>-1</sup> 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.
Medical subject headings
- Models, Molecular
- Protein Folding
- Thermodynamics
- Viral Proteins