protease-activated receptor 1, member of the class A family of seven-transmembrane G protein-coupled receptors
Protease-acted receptors (PARs) are seven-transmembrane proteins that belong to the class A G-protein coupled receptor (GPCR) family. Four different types of the protease-activated receptors have been identified: PAR1, PAR2, PAR3, and PAR4. PARs are predominantly expressed in platelets and are activated by serine proteases such as thrombin, trypsin, and tryptase. These proteases cleave the extracellular domain of the receptor to form a new N-terminus, which in turn functions as a tethered ligand. The newly-formed tethered ligand binds intramolecularly to activate the receptor and triggers G-protein binding and intracellular signaling. PAR1, PA3, and PAR4 are activated by thrombin, whereas PAR2 is activated by trypsin. The PARs are known to couple with several G-proteins including Gi (cAMP inhibitory), G12/13 (Rho and Ras activation), and Gq (calcium signaling) to activate downstream signaling messengers which induces numerous cellular and physiological effects.
Comment:also based on the structures of some class A family members with bound ligands (peptides or chemicals), agonists, or antagonists
Comment:Small-molecule chemical ligands tend to bind deeper within the receptor core, compared to a peptide ligand neurotensin, which binds towards the extracellular surface of its receptor.
Structure:3VW7: Human protease-activated receptor 1 (PAR1) bound with antagonist vorapaxar, contacts at 4A.
Jiyao W et al.(2023). "The conserved domain database in 2023.",