Folding and stability of α-helical integral membrane proteins

A review is given of the results of genetic, cell biological, biochemical, and biophysical studies of α-helical integral membrane protein folding and stability with an emphasis on connecting the results from different types of experiments in the context of the current thermodynamic formalisms. It is shown that although the data do not yield a complete picture of the energetics of interfacial association, transbilayer insertion, and lateral assembly of helical membrane spans, the advances made to date indicate strongly that the thermodynamic frameworks of Popot and Engelman and of Wimley and White can incorporate a multiplicity of experimental inputs to explain the behavior of helical membrane proteins. Close correspondence between the concept of hydrophobicity, the peptide-based free energy scales for partitioning, and the biological hydrophobicity scale derived from measurements with the eukaryotic translocon shows that the general principles that underlie the physicochemical basis for membrane protein behavior can inform both membrane biophysicists and membrane biologists.