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Biochim Biophys Acta. 2011 Dec;1814(12):1730-8. PubMed; doi 10.1016/j.bbapap.2011.08.006

Chaperonins induce an amyloid-like transformation of ovine prion protein: the fundamental difference in action between eukaryotic TRiC and bacterial GroEL.

Kiselev, G. G.; Naletova, I. N.; Sheval, E. V.; Stroylova, Y. Y.; Schmalhausen, E. V.; Haertle, T.; Muronetz, V. I.

Molecular chaperones have been shown to be involved in the processes taking place during the pathogenesis of various amyloid neurodegenerative diseases. However, contradictory literature reports suggest that different molecular chaperones can either stimulate or prevent the formation of amyloid structures from distinct amyloidogenic proteins. In the present work, we concentrated on the effects caused by two molecular chaperonins, ovine TRiC and bacterial GroEL, on the aggregation and conformational state of ovine PrP. Both chaperonins were shown to bind native PrP and to produce amyloid-like forms of ovine PrP enriched with beta-structures but, while GroEL acted in an ATP-dependent manner, TRiC was shown to cause the same effect only in the absence of Mg-ATP (i.e. in the inactive form). In the presence of chaperonin GroEL, ovine PrP was shown to form micellar particles, approximately 100-200nm in diameter, which were observed both by dynamic light scattering assay and by electron microscopy. The content of these particles was significantly higher in the presence of Mg-ATP and, only under these conditions, GroEL produced amyloid-like species enriched with beta-structures. TRiC was shown to induce the formation of amyloid fibrils observed by electron microscopy, but only in the absence of Mg-ATP. This study suggests the important role of the cytosolic chaperonin TRiC in the propagation of amyloid structures in vivo during the development of amyloid diseases and the possible role of the bacterial chaperonin GroEL, located in the intestinal microflora, in the induction of these diseases.



 


  Московский Государственный Университет имени М.В.Ломоносова



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Факультет биоинженерии и биоинформатики, комната 433.

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© 2011 Факультет биоинженерии и биоинформатики
Московского Государственного Университета имени М.В.Ломоносова


 





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