3-DIMENSIONAL MODEL OF THE HUMAN PAF RECEPTOR

The amino acid sequence analysis of the human platelet-activating fact or (PAF) receptor showed that residues thought to be important structu rally and functionally were well conserved. This suggested similaritie s of the three-dimensional structure (3D structure) between the human PAF receptor and other receptors that couple to guanine nucleotide bin ding (G) proteins. Thus, a three-dimensional model of this receptor wa s constructed using the 3D structure of bacteriorhodopsin as the refer ence protein, by means of the BIOCES[E] computer-modeling system. This model has seven alpha-helical transmembrane segments which form a cen tral core and an S-S bond between the second and third extracellular l oops. The distance of the S-S bond is about 2 Angstrom, which is thoug ht to be reasonable. In the transmembrane domain, the side chains of A sp-63, Asn-285 and Asp-289 became oriented toward the central core and form a negatively charged site. This receptor model suggests that the positively charged choline moiety of PAF is attracted to this negativ ely charged site by electrostatic forces and that PAF may induce confo rmational changes in the receptor, leading to G-protein activation.