Protein Knotting by Active Threading of Nascent Polypeptide Chain Exiting from the Ribosome Exit Channel
Pawel Dabrowski-Tumanski†‡∥, Maciej Piejko†‡∥, Szymon Niewieczerzal‡, Andrzej Stasiak*¶§, and Joanna I. Sulkowska*‡†
† Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093, Warsaw, Poland
‡ Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097, Warsaw, Poland
¶ Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland
§ Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland
J. Phys. Chem. B, Article ASAP
DOI: 10.1021/acs.jpcb.8b07634
Publication Date (Web): September 10, 2018
Copyright © 2018 American Chemical Society
*(A.S.) E-mail: Andrzej.Stasiak@unil.ch
*(J.I.S.) E-mail: j.sulkowska@cent.uw.edu.pl
This article is part of the William A. Eaton Festschrift special issue.
Abstract
The mechanism of folding of deeply knotted proteins into their native structure is still not understood. Current thinking about protein folding is dominated by the Anfinsen dogma, stating that the structure of the folded proteins is uniquely dictated by the amino acid sequence of a given protein and that the folding is driven uniquely by the energy gained from interactions between amino acids that contact each other in the native structure of the protein. The role of ribosomes in protein folding was only seen as permitting the folding to progress from the N-terminal part of nascent protein chains. We propose here that ribosomes can participate actively in the folding of knotted proteins by actively threading nascent chains emerging from the ribosome exit channels through loops formed by a synthesized earlier portion of the same protein. Our simulations of folding of deeply knotted protein Tp0624 positively verify the proposed ribosome-driven active threading mechanism leading to the formation of deeply knotted proteins.
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