Sequence divergence analysis for the prediction of seven-helix membrane protein structures: II. A 3-D model of human rhodopsin.

Abstract

A three-dimensional (3-D) model of the transmembrane domain of human rhodopsin was predicted from the sequence divergence analysis of 42 sequences of rhodopsins and visual pigments without a template. The prediction steps include multiple sequence alignment, calculation of a variability profile of the aligned sequences, use of the variability profile to identify the boundaries of transmembrane regions, their secondary structure and packing shape in a helix bundle, prediction of side-chain conformations and structure refinement. The identification of the retinal binding site was assisted by its known covalent linkage with K296. The structural features of the predicted 3-D model are in good agreement with a low resolution electron density map of bovine rhodopsin and with residues in contact with retinal as determined experimentally.