Unfolding and Translocation of Knotted Proteins by Clp Biological Nanomachines: Synergistic Contribution of Primary Sequence and Topology Revealed by Molecular Dynamics Simulations

2021 ◽  
Author(s):  
Hewafonsekage Yasan Y. Fonseka ◽  
Alex Javidi ◽  
Luiz F. L. Oliveira ◽  
Cristian Micheletti ◽  
George Stan
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Primary Sequence ◽  
And Topology ◽  
Knotted Proteins ◽  
Dynamics Simulations

scholarly journals Unfolding and Translocation of Knotted Proteins by Clp Biological Nanomachines: Synergistic Contribution of Primary Sequence and Topology Revealed by Molecular Dynamics Simulations

2021 ◽  
Author(s):  
Hewafonsekage Yasan Y. Fonseka ◽  
Alex Javidi ◽  
Luiz F. L. Oliveira ◽  
Cristian Micheletti ◽  
George Stan
Keyword(s):  
Molecular Dynamics ◽  
Protein Structure ◽  
Molecular Dynamics Simulations ◽  
Side Chain ◽  
Primary Sequence ◽  
Activation Barriers ◽  
And Topology ◽  
Knotted Protein ◽  
Knotted Proteins ◽  
Dynamics Simulations

AbstractWe use Langevin dynamics simulations to model, at atomistic resolution, how various natively–knotted proteins are unfolded in repeated allosteric translocating cycles of the ClpY ATPase. We consider proteins representative of different topologies, from the simplest knot (trefoil 31), to the three–twist 52 knot, to the most complex stevedore, 61, knot. We harness the atomistic detail of the simulations to address aspects that have so far remained largely unexplored, such as sequence–dependent effects on the ruggedness of the landscape traversed during knot sliding. Our simulations reveal the combined effect on translocation of the knotted protein structure, i.e. backbone topology and geometry, and primary sequence, i.e. side chain size and interactions, and show that the latter can even dominate translocation hindrance. In addition, we observe that, due to the interplay between the knotted topology and intramolecular contacts, the transmission of tension along the peptide chain occurs very differently from homopolymers. Finally, by considering native and non–native interactions, we examine how the disruption or formation of such contacts can affect the translocation processivity and concomitantly create multiple unfolding pathways with very different activation barriers.

scholarly journals The Role of Non-Native Interactions in the Folding of Knotted Proteins: Insights from Molecular Dynamics Simulations

Biomolecules ◽  
2013 ◽  
Vol 4 (1) ◽  
pp. 1-19 ◽  
Author(s):  
Roberto Covino ◽  
Tatjana Škrbić ◽  
Silvio Beccara ◽  
Pietro Faccioli ◽  
Cristian Micheletti
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Knotted Proteins ◽  
Dynamics Simulations

Tight knots in proteins: can they block the mitochondrial pores?

2013 ◽  
Vol 41 (2) ◽  
pp. 620-624 ◽  
Author(s):  
Piotr Szymczak
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Present Article ◽  
Protein Translocation ◽  
Cellular Membranes ◽  
Numerical Studies ◽  
Knotted Protein ◽  
Knotted Proteins ◽  
Dynamics Simulations

Proteins need to be unfolded when translocated through the pores in mitochondrial and other cellular membranes. Knotted proteins, however, might get stuck during this process since the diameter of the pore is smaller than the size of maximally tightened knot. In the present article, I briefly review the experimental and numerical studies of tight knots in proteins, with a particular emphasis on the estimates of the size of these knots. Next, I discuss the process of protein translocation through the mitochondrial pores and report the results of molecular dynamics simulations of knotted protein translocation, which show how the knot can indeed block the pore.

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