Structure and Stability of Membrane Proteins

Abstract

This chapter addresses question such as “If the hydrophobic theory of protein stability is correct, how is it possible for stable proteins to exist in nonaqueous environments where hydrophobic effects should be quantitatively less significant?” in light of the available structural and stability data on integral membrane proteins, emphasizing a comparison of these properties to those of better characterized water-soluble proteins. An important lesson from the study of membrane proteins is that water is not absolutely indispensable for the ability of proteins to adopt stable three-dimensional structures; proteins can also stably exist in nonaqueous solvents, whether in the membrane bilayer or in nonbiological systems. By definition, hydrophobic interactions are not indispensable for protein stability, because proteins with stable tertiary structures occur in nonaqueous solvents. The role of hydrophobic interactions in protein stability may be analogous to the role of disulfide bridges; whereas some proteins cannot exist without disulfide bridges, they are certainly not required by every protein. The continued study of proteins in membranes and other nonaqueous environments is fundamental to defining the contributions of all solvents to the origins of protein structure and stability.