Cotranslational folding of deeply knotted proteins

Chwastyk

2017

Sci Rep

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Using a structure-based coarse-grained model of proteins, we study the mechanism of unfolding of knotted proteins through heating. We find that the dominant mechanisms of unfolding depend on the temperature applied and are generally distinct from those identified for folding at its optimal temperature. In particular, for shallowly knotted proteins, folding usually involves formation of two loops whereas unfolding through high-temperature heating is dominated by untying of single loops. Untying the knots is found to generally precede unfolding unless the protein is deeply knotted and the heating temperature exceeds a threshold value. We then use a phenomenological model of the air-water interface to show that such an interface can untie shallow knots, but it can also make knots in proteins that are natively unknotted.

Section: Methodsmentioning

confidence: 99%

Topological transformations in proteins: effects of heating and proximity of an interface

Chwastyk

2017

Sci Rep

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“…Folding is facilitated by nascent conditions and by inclusion of certain contacts which should count as native 26 . We expect that folding the dimer is even harder and we do not attempt to study it here.…”

Section: B 1j85mentioning

confidence: 99%

“…[27][28][29] . One of the results obtained was that the probability to form a knot on folding is enhanced by on-ribosome folding 26,29 . Here, however, we do not consider folding under nascent conditions.…”

Section: Introductionmentioning

confidence: 99%

Structural entanglements in protein complexes

Chwastyk

The Journal of Chemical Physics

2017

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We consider multi-chain protein native structures and propose a criterion that determines whether two chains in the system are entangled or not. The criterion is based on the behavior observed by pulling at both temini of each chain simultaneously in the two chains. We have identified about 900 entangled systems in the Protein Data Bank and provided a more detailed analysis for several of them. We argue that entanglement enhances the thermodynamic stability of the system but it may have other functions: burying the hydrophobic residues at the interface, and increasing the DNA or RNA binding area. We also study the folding and stretching properties of the knotted dimeric proteins MJ0366, YibK and bacteriophytochrome. These proteins have been studied theoretically in their monomeric versions so far. The dimers are seen to separate on stretching through the tensile mechanism and the characteristic unraveling force depends on the pulling direction.

“…This is similar to what happens with the deeply and shallowly knotted proteins. [40][41][42] It should be noted that, when starting with conformations of group 2, there is a possibility of a definite separation of the chains (which is declared when their centers of mass are at least 200 Å apart). In fact, this happens in 42 trajectories in the example discussed.…”

Section: Folding and Thermodynamicsmentioning

confidence: 99%

Stability of structurally entangled protein dimers

2018

Proteins

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We studied stretching, folding and thermodynamic properties of structurally entangled protein dimers. The tests for entanglement involve four-terminal pulling. We study the dynamics of such pulling and contrast it with the standard two-terminal one. The two-chain entanglement is qualitatively characterized by its entangled core, which is defined as the minimal structure that is entangled. The existence of the entangled cores is found to be affecting both the mechanical and folding properties of the proteins. We also show that the folding pathways of the entangled proteins are not universal but the bottleneck is always the formation of the entangled conformation. We demonstrate that entanglement enhances thermodynamic stability.