The energy cost of polypeptide knot formation and its folding consequences

Sotelo-Campos, Juan; Wilson, Christian A. M.; Guerra Giraldez, Daniel; Bustamante, Carlos; Bustamante, Andrés; Báez, Mauricio; Floor, Martin

dc.contributor.author	Bustamante, Andrés
dc.contributor.author	Sotelo-Campos, Juan
dc.contributor.author	Guerra Giraldez, Daniel
dc.contributor.author	Floor, Martin
dc.contributor.author	Wilson, Christian A. M.
dc.contributor.author	Bustamante, Carlos
dc.contributor.author	Báez, Mauricio
dc.date.accessioned	2019-01-25T16:03:21Z
dc.date.available	2019-01-25T16:03:21Z
dc.date.issued	2017
dc.identifier.uri	https://hdl.handle.net/20.500.12866/4775
dc.description.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.	en_US
dc.language.iso	eng
dc.publisher	Springer Nature
dc.relation.ispartofseries	Nature Communications
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.rights.uri	https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject	Models, Molecular	en_US
dc.subject	Protein Folding	en_US
dc.subject	Thermodynamics	en_US
dc.subject	Bacteriophages/metabolism	en_US
dc.subject	Monte Carlo Method	en_US
dc.subject	Optical Tweezers	en_US
dc.subject	Protein Conformation	en_US
dc.subject	Protein Denaturation	en_US
dc.subject	Viral Proteins/chemistry/genetics	en_US
dc.title	The energy cost of polypeptide knot formation and its folding consequences	en_US
dc.type	info:eu-repo/semantics/article
dc.identifier.doi	https://doi.org/10.1038/s41467-017-01691-1
dc.subject.ocde	https://purl.org/pe-repo/ocde/ford#1.06.03
dc.subject.ocde	https://purl.org/pe-repo/ocde/ford#1.04.00
dc.subject.ocde	https://purl.org/pe-repo/ocde/ford#1.03.00
dc.relation.issn	2041-1723