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.

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

scholarly journals Fast leaps between millisecond confinements govern Ase1 diffusion along microtubules

2021 ◽  
Author(s):  
Łukasz Bujak ◽  
Kristýna Holanová ◽  
Antonio García Marín ◽  
Verena Henrichs ◽  
Ivan Barvík ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Cell Division ◽  
Molecular Dynamics Simulations ◽  
Interaction Potential ◽  
Electrostatic Potential ◽  
Fundamental Mode ◽  
Protein Translocation ◽  
Periodic Surface ◽  
Tubulin Dimer ◽  
Dynamics Simulations

AbstractDiffusion is the most fundamental mode of protein translocation within cells. Confined diffusion of proteins along the electrostatic potential constituted by the surface of microtubules, although modeled meticulously in molecular dynamics simulations, has not been experimentally observed in real-time. Here, we used interferometric scattering microscopy to directly visualize the movement of the microtubule-associated protein Ase1 along the microtubule surface at nanometer and microsecond resolution. We resolved millisecond confinements of Ase1 and fast leaps between these positions of dwelling preferentially occurring along the microtubule protofilaments, revealing Ase1’s mode of diffusive translocation along the microtubule’s periodic surface. The derived interaction potential closely matches the tubulin-dimer periodicity and the distribution of the electrostatic potential on the microtubule lattice. We anticipate that mapping the interaction landscapes for different proteins on microtubules, finding plausible energetic barriers of different positioning and heights, will provide valuable insights into regulating the dynamics of essential cytoskeletal processes, such as intracellular cargo trafficking, cell division, and morphogenesis, all of which rely on diffusive translocation of proteins along microtubules.

Dynamic Mechanism of Fatty Acid Transport across Cellular Membranes through FadL: Molecular Dynamics Simulations

2008 ◽  
Vol 112 (41) ◽  
pp. 13070-13078 ◽  
Author(s):  
Hanjun Zou ◽  
Mingyue Zheng ◽  
Xiaomin Luo ◽  
Weiliang Zhu ◽  
Kaixian Chen ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Fatty Acid ◽  
Molecular Dynamics Simulations ◽  
Dynamic Mechanism ◽  
Fatty Acid Transport ◽  
Acid Transport ◽  
Cellular Membranes ◽  
Dynamics Simulations

scholarly journals Collision-induced dissociation of protonated uracil water clusters probed by molecular dynamics simulations

2021 ◽  
Author(s):  
Linjie Zheng ◽  
Jérôme Cuny ◽  
Sébastien Zamith ◽  
Jean-Marc L'Hermite ◽  
Mathias Rapacioli
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Present Article ◽  
Molecular Species ◽  
Water Clusters ◽  
Collision Induced Dissociation ◽  
Chemical Information ◽  
Theoretical Support ◽  
Dynamics Simulations

Collision-induced dissociation experiments of hydrated molecular species can provide a wealth of important information. However, they often need a theoretical support to extract chemical information. In the present article, in...

Mapping the morphological identifiers of distinct conformations via the protein translocation current in nanopores

Nanoscale ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 6053-6065
Author(s):  
Mingkun Zhang ◽  
Shenbao Chen ◽  
Jinrong Hu ◽  
Qihan Ding ◽  
Linda Li ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Protein Translocation ◽  
Theoretical Method ◽  
Protein Conformations ◽  
Dynamics Simulations

A theoretical method based on molecular dynamics simulations was proposed to resolve the morphological signatures of protein conformations by orientation-modulated principle in nanopore sensing technique.

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