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

A three-dimensional (3-D) model of the transmembrane domainof human rhodopsin was predicted from the sequence divergenceanalysis of 42 sequences of rhodopsins and visual pigments withouta 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 oftransmembrane regions, their secondary structure and packingshape in a helix bundle, prediction of side-chain conformationsand structure refinement. The identification of the retinalbinding site was assisted by its known covalent linkage withK296. The structural features of the predicted 3-D model arein good agreement with a low resolution electron density mapof bovine rhodopsin and with residues in contact with retinalas determined experimentally.