[The non-functioning chaperonin GroEL stimulates protein aggregation].
To clarify the role of chaperones in the development of amyloid diseases, the interaction of the chaperonin GroEL with misfolded proteins and recombinant prions has been studied. The efficiency of the chaperonin-assisted folding of denatured glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was shown to decrease in the presence of prions. Prions are capable of binding to GroEL immobilized on Sepharose, but this does not prevent the interaction between GroEL and other denatured proteins. The sizes of individual proteins (GroEL, GAPDH, and the recombinant prion), as well as aggregates formed after their mixing, were determined by the dynamic light scattering method. It was shown that at 25 degrees C the non-functioning chaperonin (equimolar mixture of GroEL and GroES in the absence of Mg-ATP) bound prion yielding large aggregates (greater than 400 nm). The addition of Mg-ATP decreased significantly the aggregate size to 70-80 nm. On the blocking of one of the chaperonin centers by oxidized denatured GAPDH, the aggregate size increased to 1200 nm, and the addition of Mg-ATP did not prevent the aggregation. These data indicate the significant role of chaperonins in the formation of amyloid structures and demonstrate the acceleration of aggregation in the presence of functionally inactive chaperonins. The suggested model can be used for the analysis of the efficiency of antiaggregants in the system containing chaperonins.
Naletov
I N
IN
Shmal'gauzen
E V
EV
Shalova
I N
IN
Pleten'
A P
AP
Tsiriul'nikov
K
K
Ertl'
T
T
Muronets
V I
VI
D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism; D000818:Animals; D018834:Chaperonin 60 / Q000737:chemistry* / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry* / Q000378:metabolism; D011328:Prions / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011489:Protein Denaturation; D051381:Rats; D012756:Sheep
D000682:Amyloid; D018834:Chaperonin 60; D011328:Prions; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases