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Inhibition of chaperonin GroEL by a monomer of ovine prion protein and its oligomeric forms

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Abstract

The possibility of inhibition of chaperonin functional activity by amyloid proteins was studied. It was found that the ovine prion protein PrP as well as its oligomeric and fibrillar forms are capable of binding with the chaperonin GroEL. Besides, GroEL was shown to promote amyloid aggregation of the monomeric and oligomeric PrP as well as PrP fibrils. The monomeric PrP was shown to inhibit the GroEL-assisted reactivation of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The oligomers of PrP decelerate the GroEL-assisted reactivation of GAPDH, and PrP fibrils did not affect this process. The chaperonin GroEL is capable of interacting with GAPDH and different PrP forms simultaneously. A possible role of the inhibition of chaperonins by amyloid proteins in the misfolding of the enzymes involved in cell metabolism and in progression of neurodegenerative diseases of amyloid nature is discussed.

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Abbreviations

DEAE:

diethylaminoethyl

DLS:

dynamic light scattering

EDTA:

ethylenediaminetetraacetate

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

HEPES:

4-(2hydroxyethyl)-1-piperazinethanesulfonic acid

β-ME:

β-mercaptoethanol

MOPS:

3-[N-morpholino]propanesulfonic acid

PBST:

phosphate-buffered saline containing 0.05% Tween-20

PrP:

prion protein

ThT:

thioflavin T

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Correspondence to V. I. Muronetz.

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Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM16-235, September 12, 2016.

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Kudryavtseva, S.S., Stroylova, Y.Y., Zanyatkin, I.A. et al. Inhibition of chaperonin GroEL by a monomer of ovine prion protein and its oligomeric forms. Biochemistry Moscow 81, 1213–1220 (2016). https://doi.org/10.1134/S0006297916100199

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  • DOI: https://doi.org/10.1134/S0006297916100199

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