Role of Aromatic Localization in the Gating Process of a Potassium Channel

Position of the transmembrane aromatic residues of the KirBac1.1 potassium channel shifts from an even distribution in the closed state toward the membrane/solute interface in the open state model. This is the first example of an integral membrane protein making use of the observed preference for transmembrane aromatic residues to reside at the interfaces. The process of aromatic localization is proposed as a means of directing and stabilizing structural changes during conformational transitions within the transmembrane region of integral membrane proteins. All-atom molecular dynamics simulations of the open and closed conformers in a membrane environment have been carried out to take account of the interactions between the aromatic residues and the lipids, which may be involved in the conformational change, e.g., the gating of the channel.

Despite the steady increase in the number of integral membrane proteins (IMP) in the Protein Data Bank and the recent success of computational studies on biological channels (1), there is still a relatively poor understanding of the extent and nature of the interactions between IMP and the surrounding lipids, and more importantly, about the functional role these interactions might have in processes such as gating and modulation. This communication reports, to our knowledge, the first example of an IMP making use of the observed preference for transmembrane aromatic residues that reside at the interfaces. The process of aromatic localization is proposed as a means of directing and stabilizing structural changes during conformational transitions within the transmembrane region of KirBac. Multiple nanosecond molecular simulations are employed to establish a qualitative picture of the intermolecular interactions between a lipid bilayer and the aromatic residues of a membrane protein for which a high resolution x-ray closed structure (2) and an open model (3–4) are available (Fig. 1).