Three-dimensional model of the human PAF receptor

• Published in: Journal of lipid mediators and cell signalling Vol. 9; no. 3; p. 185
• Main Authors: Kajihara, A, Komooka, H, Kamiya, K, Yoneda, T, Yoneda, S, Nakamura, M, Shimizu, T, Umeyama, H
• Format: Journal Article
• Language: English
• Published: Netherlands 01-05-1994
• Subjects: Amino Acid Sequence; Choline - chemistry; Computer Simulation; Humans; Models, Molecular; Molecular Sequence Data; Phosphorylcholine - chemistry; Platelet Membrane Glycoproteins - chemistry; Protein Conformation; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Sequence Homology, Amino Acid; Structure-Activity Relationship
• ISSN: 0929-7855

The amino acid sequence analysis of the human platelet-activating factor (PAF) receptor showed that residues thought to be important structurally and functionally were well conserved. This suggested similarities of the three-dimensional structure (3D structure) between the human PAF receptor and other receptors that couple to guanine nucleotide binding (G) proteins. Thus, a three-dimensional model of this receptor was constructed using the 3D structure of bacteriorhodopsin as the reference protein, by means of the BIOCES[E] computer-modeling system. This model has seven alpha-helical transmembrane segments which form a central core and an S-S bond between the second and third extracellular loops. The distance of the S-S bond is about 2 A, which is thought to be reasonable. In the transmembrane domain, the side chains of Asp-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 negatively charged site by electrostatic forces and that PAF may induce conformational changes in the receptor, leading to G-protein activation.