Recombinant mouse 18 kDa peripheral-type benzodiazepine receptor (PBR) protein was overexpressed in Escherichia coli and isolated using a His Bind metal chelation resin. Recombinant PER protein was purified with sodium dodecyl sulfate and reincorporated into Liposomes using Bio-Beads SM2 as a detergent removing agent. Negative staining of the reconstituted PER samples, examined by electron microscopy, showed the formation of proteoliposomes. Freeze-fracture of these proteoliposomes revealed the presence of transmembranous particles of an average size of 3.5 +/- 0.25 nm, consistent with the presence of a monomeric form of the recombinant PER protein. The reconstituted protein exhibited the ability to bind both the PER drug Ligand isoquinoline carboxamide PK 11195 and cholesterol with nanomolar affinities. These data suggest that a PER monomer is the minimal functional unit, binding drug ligands and cholesterol.