Serine and threonine residues bend alpha-helices in the chi(1) = g(-) conformation

The relationship between the Ser, Thr, and Cys side-chain conformation (chi (1) = g(-), t, g(+)) and the main-chain conformation (phi and psi angles) has been studied in a selection of protein structures that contain alpha -h elices. The statistical results show that the g(-) conformation of both Ser and Thr residues decreases their phi angles and increases their psi angles relative to Ala, used as a control. The additional hydrogen bond formed be tween the O-gamma atom of Ser and Thr and the i-3 or i-4 peptide carbonyl o xygen induces or stabilizes a bending angle in the helix 3-4 degrees larger than for Ala. This is of particular significance for membrane proteins. In corporation of this small bending angle in the transmembrane alpha -helix a t one side of the cell membrane results in a significant displacement of th e residues located at the other side of the membrane. We hypothesize that l ocal alterations of the rotamer configurations of these Ser and Thr residue s may result in significant conformational changes across transmembrane hel ices, and thus participate in the molecular mechanisms underlying transmemb rane signaling. This finding has provided the structural basis to understan d the experimentally observed influence of Ser residues on the conformation al equilibrium between inactive and active states of the receptor, in the n eurotransmitter subfamily of G protein-coupled receptors.