Accelerated protein aggregation induced by macrophage migration inhibitory factor under heat stress conditions.
Kinetics of thermal aggregation of model protein substrates (glycogen phosphorylase b from rabbit skeletal muscle and yeast alcohol dehydrogenase) were investigated under heat stress conditions (41-48 degrees C) in the presence of macrophage migration inhibitory factor (MIF), a heat-stable hydrophobic protein (12.5 kD). Anti-chaperone MIF activity found by turbidimetry manifests itself in significantly accelerated protein aggregation and increased limiting value of apparent optical absorption at 360 nm and t --> infinity in the sub-stoichiometric range of MIF concentrations. The aggregation kinetics is shown to have cooperative character. Possible reversibility of aggregation after removal of denaturing conditions was demonstrated using alcohol dehydrogenase aggregation at a temperature close to the physiological level (41.5 degrees C). This reversibility is caused by solubility of aggregates and stabilization of oligomeric structure of the substrate as a result of MIF binding to the partially denatured protein. The data suggest that in spite of distinct anti-chaperone effect, the chaperone-like activity of MIF can be observed in the case of heat stress removal and restoration of the system to normal conditions.
Cherepkova
O A
OA
Bach Institute of Biochemistry, Russian Academy of Sciences, 119071 Moscow, Russia.
Lyutova
E M
EM
Eronina
T B
TB
Gurvits
B Ya
BY
D000426:Alcohol Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001923:Brain Chemistry; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D024982:Glycogen Phosphorylase, Muscle Form / Q000737:chemistry / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D006358:Hot Temperature; D007700:Kinetics; D008263:Macrophage Migration-Inhibitory Factors / Q000737:chemistry* / Q000302:isolation & purification / Q000502:physiology; D018482:Muscle, Skeletal / Q000201:enzymology; D018384:Oxidative Stress; D011817:Rabbits; D012441:Saccharomyces cerevisiae / Q000201:enzymology
D006360:Heat-Shock Proteins; D008263:Macrophage Migration-Inhibitory Factors; D000426:Alcohol Dehydrogenase; D024982:Glycogen Phosphorylase, Muscle Form