Conformational States and Thermodynamics of α-Lactalbumin Bound to Membranes: A Case Study of the Effects of pH, Calcium, Lipid Membrane Curvature and Charge

The study of the conformational changes of bovine α-lactalbumin, switching from soluble states to membrane-bound states, deepens our knowledge of the behaviour of amphitropic proteins. The binding and the membrane-bound conformations of α-lactalbumin are highly sensitive to environmental factors, like calcium and proton concentrations, curvature and charge of the lipid membrane. The interactions between the protein and the membrane result from a combination of hydrophobic and electrostatic interactions and the respective weights of these interactions depend on the physicochemical conditions. As inferred by macroscopic as well as residue-level methods, the conformations of the membrane-bound protein range from native-like to molten globule-like states. However, the regions anchoring the protein to the membrane are similar and restricted to amphiphilic α-helices. H/2H-exchange experiments also yield residue-level data that constitute comprehensive information providing a new point of view on the thermodynamics of the interactions between the protein and the membrane.