The energy cost of polypeptide knot formation and its folding consequences

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

doi:10.1038/s41467-017-01691-1

The energy cost of polypeptide knot formation and its folding consequences

Journal Article · Fri Nov 17 00:00:00 EST 2017 · Nature Communications

DOI:https://doi.org/10.1038/s41467-017-01691-1· OSTI ID:1624057

Bustamante, Andrés ^[1]; Sotelo-Campos, Juan ^[2]; Guerra, Daniel G. ^[3]; Floor, Martin ^[4]; Wilson, Christian A. M. ^[4]; Bustamante, Carlos ^[5]; Báez, Mauricio ^[4]

Universidad de Chile, Santos Dumont 964, Independencia, Santiago (Chile). Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas; DOE/OSTI
Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martin de Porras (Peru). Departamento Académico de Ciencias Exactas, Facultad de Ciencias y Filosofía
Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martin de Porras (Peru). Laboratorio de Moléculas Individuales, Facultad de Ciencias y Filosofía
Universidad de Chile, Santos Dumont 964, Independencia, Santiago (Chile). Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas
Universidad Peruana Cayetano Heredia, Av. Honorio Delgado 430, San Martin de Porras (Peru). Laboratorio de Moléculas Individuales, Facultad de Ciencias y Filosofía; Univ. of California, Berkeley, CA (United States). Department of Molecular and Cell Biology, Department of Physics and Department of Chemistry, Kavli Energy Nanoscience Institute, and Howard Hughes Medical Institute

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1624057

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 8; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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