N-terminal protein recognition by supramolecular synthons

Abstract

This research investigate the biomolecular recognition capabilities of WPCTX, an anionic phosphocavitand. Cocrystallization trials of WPCTX and two different model proteins were performed. X-ray crystallography was used to elucidate the structures of the resulting crystals. NMR spectroscopy was used to characterize the protein – macrocycle interactions in solution. WPCTX bound arginine residues in lysozyme in a trigonal cocrystal form. Three related cocrystal forms of RSL – WPCTX revealed N-terminal binding across a variety of crystallization conditions. MK-RSL, a mutant of RSL containing an extended N-terminus with a Met-Lys motif showed further N-terminal binding with WPCTX. The macrocycle in RSL and MK-RSL cocrystals, formed clusters that mediated protein assembly. These results identify a synthetic ligand capable of N-terminal recognition as well as self-assembly (cluster formation) furthering our knowledge as to how supramolecular synthons may aid protein assembly