The relationship between the Ser, Thr, and Cys side-chain conformation (χ1 = g-, t, g+) and the main-chain conformation (φ and ψ angles) has been studied in a selection of protein structures that contain α-helices. The statistical results show that the g- conformation of both Ser and Thr residues decreases their φ angles and increases their ψ angles relative to Ala, used as a control. The additional hydrogen bond formed between the O(γ) atom of Ser and Thr and the i-3 or i-4 peptide carbonyl oxygen induces or stabilizes a bending angle in the helix 3-4°larger than for Ala. This is of particular significance for membrane proteins. Incorporation of this small bending angle in the transmembrane α-helix at one side of the cell membrane results in a significant displacement of the residues located at the other side of the membrane. We hypothesize that local alterations of the rotamer configurations of these Ser and Thr residues may result in significant conformational changes across transmembrane helices, and thus participate in the molecular mechanisms underlying transmembrane signaling. This finding has provided the structural basis to understand the experimentally observed influence of Ser residues on the conformational equilibrium between inactive and active states of the receptor, in the neurotransmitter subfamily of G protein-coupled receptors.
|Publication status||Published - 1 Jan 2000|