Key result
Thrombin-cleaved PAR4 exhibited a 2-fold increase in t 1/2 values for four histidine residues (p > 0.01), demonstrating decreased solvent accessibility upon thrombin treatment.
Why the study?
Numerous studies have focused on signaling pathways mediated by protease-activated receptors, but the structural basis for initiation of these pathways was unknown.
Population
Purified PAR4 isolated without stabilizing modifications
Comparison
Apo vs thrombin-activated or activation peptide-treated PAR4
Design
In vitro biophysical study using histidine hydrogen-deuterium exchange
Authors
Loading...
May enable PAR4 structural studies; leaves open translation to cardiovascular PAR-targeted therapies.
Effect estimate: 2-fold increase
p-value: p=> 0.01
This study establishes a strategy for PAR4 expression and purification, providing the first biophysical evidence of conformational changes during its tethered ligand activation mechanism.
Fuente et al. (2020) studied this question. Thrombin activation vs. Apo or unstimulated PAR4 was evaluated on t 1/2 for histidine residues (solvent accessibility) (2-fold increase, p=> 0.01). Thrombin-cleaved PAR4 exhibited a 2-fold increase in t 1/2 values for four histidine residues (p > 0.01), demonstrating decreased solvent accessibility upon thrombin treatment.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: