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Issue 14, 2014
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Effect of interactions with the chaperonin cavity on protein folding and misfolding

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Abstract

Recent experimental and computational results have suggested that attractive interactions between a chaperonin and an enclosed substrate can have an important effect on the protein folding rate: it appears that folding may even be slower inside the cavity than under unconfined conditions, in contrast to what we would expect from excluded volume effects on the unfolded state. Here we examine systematically the dependence of the protein stability and folding rate on the strength of such attractive interactions between the chaperonin and substrate, by using molecular simulations of model protein systems in an idealised attractive cavity. Interestingly, we find a maximum in stability, and a rate which indeed slows down at high attraction strengths. We have developed a simple phenomenological model which can explain the variations in folding rate and stability due to differing effects on the free energies of the unfolded state, folded state, and transition state; changes in the diffusion coefficient along the folding coordinate are relatively small, at least for our simplified model. In order to investigate a possible role for these attractive interactions in folding, we have studied a recently developed model for misfolding in multidomain proteins. We find that, while encapsulation in repulsive cavities greatly increases the fraction of misfolded protein, sufficiently strong attractive protein–cavity interactions can strongly reduce the fraction of proteins reaching misfolded traps.

Graphical abstract: Effect of interactions with the chaperonin cavity on protein folding and misfolding

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Publication details

The article was received on 09 Jul 2013, accepted on 22 Aug 2013 and first published on 27 Sep 2013


Article type: Paper
DOI: 10.1039/C3CP52872C
Phys. Chem. Chem. Phys., 2014,16, 6358-6366

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    Effect of interactions with the chaperonin cavity on protein folding and misfolding

    A. Sirur, M. Knott and R. B. Best, Phys. Chem. Chem. Phys., 2014, 16, 6358
    DOI: 10.1039/C3CP52872C

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