Fig. 5: HTRA1 assembly and activity in the presence of supramolecular ligands.
From: Rational correction of pathogenic conformational defects in HTRA1
a Structure of guanidiniocarbonyl pyrroles (GCPs). b β-casein degradation by wt and mutant HTRA1 (1 µM) in the absence (Ctrl) or presence of MK2 (2.5 mM). Left panels: activity of HTRA1 wt or R274Q. Graphs depict the relative loss of β-casein signal (mean ± SD of 2 [MK2] or 3 [Ctrl] independent experimental data). Right panel: relative activity of wt or mutant HTRA1. The rates of β-casein cleavage are presented as the maximum gradient of β-casein degradation after acceleration and before substrate exhaustion (mean ± SD of 2 [MK2, TNMK09, TNMK27] or 3 [Ctrl, MK1] independent experimental data; empty circles: individual data points). c Oligomeric states of wt and mutant HTRA1 in the absence or presence of MK2 analyzed via NMR DOSY experiments. Inlet: 25 µM R274Q (monomeric), 100 µM R274Q (trimeric) and 25 µM R274Q + MK2 2.5 mM (mean ± SD of 6 technical replicates). The slope in the Stejskal-Tanner plots represents the negative diffusion coefficient. Small molecules exhibit a larger diffusion coefficient and thus a steeper slope, while large molecules with a smaller diffusion coefficient show a shallower slope. Source data are provided as a Source Data file.
