Role of the conservative interhelical hydrogen bond Ser74–Trp158 at the cholesterol binding site in the conformational stability of the β2-adrenergic receptor: Molecular dynamics simulation

Abstract

To explore the role of the evolutionary conservative interhelical hydrogen bond (IHB) Ser74–Trp158 in maintaining the conformational stability of the β₂-adrenergic receptor, this work employs the molecular dynamics technique to study the conformational behavior of the receptor in the presence and absence of IHB. It is found that the Ser74–Trp158 IHB cleavage can cause further conformational transformations (helix shifts, change in the conformation of some amino acid residues). The S74A mutation in the receptor, which makes the IHB formation impossible, also leads to conformational changes: in the presence of cholesterol the mutated receptor takes a conformation close to the active form.