Аннотация:The detailed mechanism of heatinducedaggregation of bovine liver glutamate dehydrogenase (GDH) has been studied. The initial stages of the aggregation process at50 °C were investigated using analytical ultracentrifugation. The sedimentation velocity analysis showed that the native protein at the concentration of 0.2 mg/mLcontained hexameric GDH and larger native associates. The samples preheated at 50 °C during 3 min contained the oligomeric forms of larger size than in the nativesample, along with hexameric GDH. Further heating (5 min) produced the dissociated forms smaller than hexamers, although the previous oligomers and the nativeprotein remained. The thermal treatment up to 10 min resulted in the loss of 83% of protein due to precipitation of large aggregates. These data allowed us to refine themechanism of the heatinducedGDH aggregation studied in our laboratory. GDH denatures upon heating with the formation of molten globulelikeintermediate [1].These minor structural changes are apparently enough to initiate protein aggregation. The irreversible dissociation step occurs after unfolding. The further growth ofaggregates proceeds by attachment of dissociated forms to the existing associates and by the aggregateaggregatesticking