Title

Construction of a 3D Model of the Cannabinoid CB1 Receptor: Determination of Helix Ends and Helix Orientation

Document Type

Article

Publication Date

5-1995

Abstract

The goal of this study was to determine the ends and orientations of the seven transmembrane helices of the cannabinoid (CB1) receptor, a G-protein coupled receptor (GPCR). After initial sequence alignment, Fourier transform methods were used with the nPRIFT hydrophobicity scale and with a variability profile to calculate the alpha-helical periodicity (AP) in the primary amino acid sequence of the human CB1 receptor and of its alignment. AP plots were used to identify the amino acids which comprise each of the seven CB1 transmembrane helices. An intracellular α helix extension of Helix 7 was characterized by analyzing the relative direction of variability and hydrophobic moment vectors. Variability moment vectors were then used to delineate the orientation of each helix in the membrane. Based upon these vector calculations, a tentative helix bundle arrangement was obtained. This arrangement is largely consistent with the proposed transmembrane helix bundle arrangement in rhodopsin, a GPCR.