Figure 6: Ubiquitylation impairs the folding reversibility of proteins and induces formation of amyloid-like fibrils.
From: The unexpected role of polyubiquitin chains in the formation of fibrillar aggregates
(a) Schematic diagram of ubiquitylated proteins. (b) Differential scanning calorimetry (DSC) traces of calmodulin (CaM) (left upper) and FKBP12 (right upper), showing that the thermal unfolding of these proteins is reversible. DSC traces of Ub6-CaM (left middle), Ub6-FKBP12 (right middle), Ub-CaM (left lower) and Ub-FKBP12 (right lower), indicating that the thermal unfolding of ubiquitylated proteins is irreversible. Black traces represent initial heating and red traces show reheating. (c) Fibril formation of sheared Ub-CaM (left upper, red), Ub6-CaM (left upper, black), Ub-FKBP12 (left lower, red) and Ub6-FKBP12 (left lower, black) as followed by ThT fluorescence. Comparative analysis of the fibril formation kinetics of ubiquitylated CaM (right upper) and FKBP12 (right lower) with transition temperature. Shear stress was applied as an agitation at a rotational speed of 25 s−1. Rate constants were obtained by fitting the data to first-order kinetics. The values represent the average of two independent experiments. Error bars, the standard error of the mean. *P<0.05 (Student’s t-test).
