A novel computational method for predicting the transmembrane structure ofG-protein coupled receptors: Application to human C5aR and C3aR

A novel algorithm was applied to the sequences of bacteriorhodopsin (BRh), of rhodopsin (Rh), and of the two human anaphylatoxin receptors. C5a-recept or (hC5aR) and C3a-receptor (hC3aR), that predicts their transmembrane doma ins (TMD) according to energy criteria alone, on the basis of their sequenc es and a template structure for each. Two consecutive criteria were applied for the predictions: the first is hydrophobicity of a sequence of residues , which determines the candidate stretches of residues that form one of the transmembrane helices. The second criterion is an energy function composed of inter residue contact energies, of hydrophobic contributions due to mem brane exposure and of the interactions of a few residues with the phospholi pid head groups. The sequence of candidate residues for each helix is longe r than that of the template, and is finally determined by threading each of the candidate stretches on each of the template helices and evaluating the energy for all possible configurations, Contact energies between residues were taken from a database (Miyazawa S and Jernigan RL (1996) J Mol Biol 25 6 623-44). The algorithm predicts well the TMD structure of BRh based on it s own template, and the TMD structure of Rh conforms well with the model of Baldwin ct nl(Baldwin JM Schertler GFX and Unger VM (1997) J Biol Chem 272 144-64), Results for the construction of the TMD of hC5aR and hC3aR were c ompared, employing the template structure of Rh. Most of the results for th ese receptors are in accord with alignments and with mutation experiments o n hC5aR and hC3aR. The predictions may serve as a basis for future mutagene sis experiments of these receptors.