Most proteins, in order to perform their biological function, have to fold to a compact native state. The increasing number of knotted and slipknotted proteins identified suggests that proteins are able to manoeuvre around topological barriers during folding. In the present article, we review the current progress in elucidating the knotting process in proteins. Although we concentrate on theoretical approaches, where a knotted topology can be unambiguously detected, comparison with experiments is also reviewed. Numerical simulations suggest that the folding process for small knotted proteins is composed of twisted loop formation and then threading by either slipknot geometries or flipping. As the size of the knotted proteins increases, particularly for more deeply threaded termini, the prevalence of traps in the free energy landscape also increases. Thus, in the case of longer knotted and slipknotted proteins, the folding mechanism is probably supported by chaperones. Overall, results imply that knotted proteins can be folded efficiently and survive evolutionary pressure in order to perform their biological functions.
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Conference Article|
March 21 2013
Knotting pathways in proteins
Joanna I. Sułkowska;
Joanna I. Sułkowska
1
*Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
†Center for Theoretical Biological Physics, University of California San Diego, 9500 Gilman Drive, San Diego, CA 92037, U.S.A.
1To whom correspondence should be addressed (emailjsulkowska@chem.uw.edu.pl).
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Jeffrey K. Noel;
Jeffrey K. Noel
‡Center for Theoretical Biological Physics, Rice University, 6100 Main Street, Houston, TX 77005, U.S.A.
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César A. Ramírez-Sarmiento;
César A. Ramírez-Sarmiento
§Departamento de Biología, Facultad de Ciencias, Universidad de Chile, Las Palmeras 3425, Casilla 6553, Santiago, Chile
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Eric J. Rawdon;
Eric J. Rawdon
∥Department of Mathematics, University of St. Thomas, 2115 Summit Avenue, St. Paul, MN 55105, U.S.A.
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Kenneth C. Millett;
Kenneth C. Millett
¶Department of Mathematics, University of California Santa Barbara, 552 University Road, Santa Barbara, CA 93106, U.S.A.
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José N. Onuchic
José N. Onuchic
‡Center for Theoretical Biological Physics, Rice University, 6100 Main Street, Houston, TX 77005, U.S.A.
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Publisher: Portland Press Ltd
Received:
November 21 2012
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem Soc Trans (2013) 41 (2): 523–527.
Article history
Received:
November 21 2012
Citation
Joanna I. Sułkowska, Jeffrey K. Noel, César A. Ramírez-Sarmiento, Eric J. Rawdon, Kenneth C. Millett, José N. Onuchic; Knotting pathways in proteins. Biochem Soc Trans 1 April 2013; 41 (2): 523–527. doi: https://doi.org/10.1042/BST20120342
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