A Stevedore's Protein Knot

Overview

Journal PLoS Comput Biol

Specialty Biology

Date 2010 Apr 7

PMID 20369018

Citations 75

Authors

Daniel Bolinger

Joanna I Sulkowska

Hsiao-Ping Hsu

Leonid A Mirny

Mehran Kardar

Jose N Onuchic

Peter Virnau

Affiliations

Soon will be listed here.

Abstract

Protein knots, mostly regarded as intriguing oddities, are gradually being recognized as significant structural motifs. Seven distinctly knotted folds have already been identified. It is by and large unclear how these exceptional structures actually fold, and only recently, experiments and simulations have begun to shed some light on this issue. In checking the new protein structures submitted to the Protein Data Bank, we encountered the most complex and the smallest knots to date: A recently uncovered alpha-haloacid dehalogenase structure contains a knot with six crossings, a so-called Stevedore knot, in a projection onto a plane. The smallest protein knot is present in an as yet unclassified protein fragment that consists of only 92 amino acids. The topological complexity of the Stevedore knot presents a puzzle as to how it could possibly fold. To unravel this enigma, we performed folding simulations with a structure-based coarse-grained model and uncovered a possible mechanism by which the knot forms in a single loop flip.

Citing Articles

Conformational and Structural Characterization of Knotted Proteins.

Jeanne Dit Fouque K, Molano-Arevalo J, Leng F, Fernandez-Lima F Biochemistry. 2024; 63(18):2293-2299.

PMID: 39189377 PMC: 11790308. DOI: 10.1021/acs.biochem.4c00218.

Theta-curves in proteins.

Dabrowski-Tumanski P, Goundaroulis D, Stasiak A, Rawdon E, Sulkowska J Protein Sci. 2024; 33(9):e5133.

PMID: 39167036 PMC: 11337915. DOI: 10.1002/pro.5133.

Is There a Functional Role for the Knotted Topology in Protein UCH-L1?.

Ferreira S, Sriramoju M, Hsu S, Faisca P, Machuqueiro M J Chem Inf Model. 2024; 64(17):6827-6837.

PMID: 39045738 PMC: 11388461. DOI: 10.1021/acs.jcim.4c00880.

Are there double knots in proteins? Prediction and verification based on TrmD-Tm1570 fusion from .

Perlinska A, Nguyen M, Pilla S, Staszor E, Lewandowska I, Bernat A Front Mol Biosci. 2024; 10:1223830.

PMID: 38903539 PMC: 11187310. DOI: 10.3389/fmolb.2023.1223830.

A Marcus-Type Inverted Region in the Translocation Kinetics of a Knotted Protein.

Tripathi P, Mehrafrooz B, Aksimentiev A, Jackson S, Gruebele M, Wanunu M J Phys Chem Lett. 2023; 14(47):10719-10726.

PMID: 38009629 PMC: 11176711. DOI: 10.1021/acs.jpclett.3c02183.

References

Mallam A, Jackson S . A comparison of the folding of two knotted proteins: YbeA and YibK. J Mol Biol. 2006; 366(2):650-65. DOI: 10.1016/j.jmb.2006.11.014. View

Virnau P, Mirny L, Kardar M . Intricate knots in proteins: Function and evolution. PLoS Comput Biol. 2006; 2(9):e122. PMC: 1570178. DOI: 10.1371/journal.pcbi.0020122. View

van Roon A, Loening N, Obayashi E, Yang J, Newman A, Hernandez H . Solution structure of the U2 snRNP protein Rds3p reveals a knotted zinc-finger motif. Proc Natl Acad Sci U S A. 2008; 105(28):9621-6. PMC: 2474504. DOI: 10.1073/pnas.0802494105. View

Mallam A, Jackson S . Folding studies on a knotted protein. J Mol Biol. 2005; 346(5):1409-21. DOI: 10.1016/j.jmb.2004.12.055. View

Mallam A, Onuoha S, Grossmann J, Jackson S . Knotted fusion proteins reveal unexpected possibilities in protein folding. Mol Cell. 2008; 30(5):642-8. DOI: 10.1016/j.molcel.2008.03.019. View

Clementi C, Nymeyer H, Onuchic J . Topological and energetic factors: what determines the structural details of the transition state ensemble and "en-route" intermediates for protein folding? An investigation for small globular proteins. J Mol Biol. 2000; 298(5):937-53. DOI: 10.1006/jmbi.2000.3693. View

Wallin S, Zeldovich K, Shakhnovich E . The folding mechanics of a knotted protein. J Mol Biol. 2007; 368(3):884-93. PMC: 2692925. DOI: 10.1016/j.jmb.2007.02.035. View

Sulkowska J, Sulkowski P, Onuchic J . Dodging the crisis of folding proteins with knots. Proc Natl Acad Sci U S A. 2009; 106(9):3119-24. PMC: 2651233. DOI: 10.1073/pnas.0811147106. View

Murzin A, Brenner S, Hubbard T, Chothia C . SCOP: a structural classification of proteins database for the investigation of sequences and structures. J Mol Biol. 1995; 247(4):536-40. DOI: 10.1006/jmbi.1995.0159. View

10.

Sulkowska J, Sulkowski P, Szymczak P, Cieplak M . Tightening of knots in proteins. Phys Rev Lett. 2008; 100(5):058106. DOI: 10.1103/PhysRevLett.100.058106. View

11.

Lua R, Grosberg A . Statistics of knots, geometry of conformations, and evolution of proteins. PLoS Comput Biol. 2006; 2(5):e45. PMC: 1463020. DOI: 10.1371/journal.pcbi.0020045. View

12.

Humphrey W, Dalke A, Schulten K . VMD: visual molecular dynamics. J Mol Graph. 1996; 14(1):33-8, 27-8. DOI: 10.1016/0263-7855(96)00018-5. View

13.

King N, Yeates E, Yeates T . Identification of rare slipknots in proteins and their implications for stability and folding. J Mol Biol. 2007; 373(1):153-66. DOI: 10.1016/j.jmb.2007.07.042. View

14.

Huang L, Makarov D . Translocation of a knotted polypeptide through a pore. J Chem Phys. 2008; 129(12):121107. DOI: 10.1063/1.2968554. View

15.

Schmidberger J, Wilce J, Weightman A, Whisstock J, Wilce M . The crystal structure of DehI reveals a new alpha-haloacid dehalogenase fold and active-site mechanism. J Mol Biol. 2008; 378(1):284-94. DOI: 10.1016/j.jmb.2008.02.035. View

16.

Fersht A . From the first protein structures to our current knowledge of protein folding: delights and scepticisms. Nat Rev Mol Cell Biol. 2008; 9(8):650-4. DOI: 10.1038/nrm2446. View

17.

Dzubiella J . Sequence-specific size, structure, and stability of tight protein knots. Biophys J. 2009; 96(3):831-9. PMC: 2716640. DOI: 10.1016/j.bpj.2008.10.019. View

18.

Yeates T, Norcross T, King N . Knotted and topologically complex proteins as models for studying folding and stability. Curr Opin Chem Biol. 2007; 11(6):595-603. PMC: 2179896. DOI: 10.1016/j.cbpa.2007.10.002. View

19.

Berman H, Westbrook J, Feng Z, Gilliland G, Bhat T, Weissig H . The Protein Data Bank. Nucleic Acids Res. 1999; 28(1):235-42. PMC: 102472. DOI: 10.1093/nar/28.1.235. View

20.

Mansfield M . Are there knots in proteins?. Nat Struct Biol. 1994; 1(4):213-4. DOI: 10.1038/nsb0494-213. View