Membrane Protein Structure and Stability: Implications of the First Crystallographic Analyses

Abstract

Beyond their diverse and essential biological functions, membrane proteins provide an important opportunity for examining the structural and energetic basis of protein folding and stability. In contrast to water-soluble proteins, the tertiary structures of integral membrane proteins are adopted in the predominantly nonaqueous and apolar environment of the lipid bilayer. Consequently, hydrophobic interactions, believed to contribute substantially to the stability of water-soluble proteins (Kauz-mann, 1959; Tanford, 1980; Dill, 1990a), should play a less significant role in the stabilization of integral membrane proteins (Engelman, 1982). Nevertheless, membrane proteins do adopt stable tertiary structures and maintain their biological functions under the same cellular growth conditions as water-soluble proteins. To rationalize the apparent contradiction that membrane proteins can fold stably despite the diminished significance of hydrophobic interactions, speculation has arisen that “there is something basically different about how membrane proteins fold relative to most other proteins” (Zubay, 1983). This chapter will survey the structural characteristics of membrane proteins of known three-dimensional structures, with emphasis on a comparison of general structural features observed in both water-soluble and membrane proteins. The purpose of this comparison is to assess whether membrane proteins and water-soluble proteins actually do exhibit fundamentally different types of structural organization. As the following discussion indicates, it appears that this is not the case. Despite the difference in polarity of the surrounding environment, membrane proteins and water-soluble proteins seem to represent variations on common structural themes, differing primarily in the polarity of the residues on the protein surface (Rees et al., 1989a,b).