Lateral association of transbilayer alpha-helices

Membrane protein folding and oligomerization often involve interactions between lipid solvated monomeric alpha-helices, and further associations of the helices into higher order states. The two states of the simplest example of this equilibrium, monomers and a homodimer, are cartooned below.

The formation of the dimer of helices results in an increase of helix-helix and lipid-lipid interactions and a loss of helix-lipid interactions. The entropy of the lipids is expected to increase, as depicted by the blue lipids released upon dimerization; the entropy of the helices is expected to decrease. The value of the equilibrium constant will depend on the magnitudes of these entropic terms and on the enthalpic terms that arise from the detailed helix-helix, helix-lipid , and lipid-lipid contacts. Further, changes in helix associations, for example by ratations to a different helix interface, may be a part of receptor signaling, channel gating, or other functions in membranes.

Therefore, we have worked to define features and energies that arise in helix interactions, including packing, hydrogen bonding, and lipid effects. We have found motifs, such as GxxxG, developed methods, such as TOXCAT and GALLEX, and exploited computational modleing. We continue to use a range of biophysical and biochemical methods in our studies.