Autocatalytic Cleavage of the EMR2 Receptor Occurs at a Conserved G Protein-coupled Receptor Proteolytic Site Motif

摘要: Post-translational cleavage at the G protein-coupled receptor proteolytic site (GPS) has been demonstrated in many class B2 receptors as well other cell surface proteins such polycystin-1. However, mechanism of GPS proteolysis never elucidated. Here we have characterized human EMR2 and identified molecular process GPS. Proteolysis highly conserved His-Leu↓Ser518 can occur inside endoplasmic reticulum compartment, resulting two protein subunits that associate noncovalently a heterodimer. Site-directed mutagenesis P+1 (Ser518) shows an absolute requirement Ser, Thr, or Cys residue for efficient proteolysis. Substitution P-2 His to amino acids produces slow processing precursor proteins, which spontaneously hydrolyze defined cell-free system. Further biochemical characterization indicates is mediated by autocatalytic intramolecular reaction similar employed N-terminal nucleophile hydrolases, are known activate themselves self-catalyzed cis-proteolysis. We propose here autoproteolytic represents paradigm motif-containing suggest these belong subfamily hydrolases.