Chapter 4 Structural and Thermodynamic Aspects of the Transfer of Proteins into and across Membranes

This chapter discusses the hydrophobicity concept and the various hydrophobicity scales that circulate in the literature. It deals with signal sequences and transmembrane segments, thus preparing the ground for a discussion of global models of protein export and membrane protein biogenesis. The concept of a hydrophobic effect, a tendency for nonpolar molecules or parts of molecules in aqueous solution to aggregate to reduce the nonpolar surface area exposed to water, has an immediate intuitive appeal, and it has been a central idea in many attempts to come to grips with the thermodynamics of protein structure. As most of the hydrophobicity scales in the literature agree in broad terms (be they empirical or statistical), most scales will yield similar results in any particular application. The central hydrophobic core is the most outstanding signature of a signal sequence. Proteins can bind to membranes in many ways. One useful distinction is between intrinsic and extrinsic membrane proteins, denoting, respectively, proteins spanning the nonpolar hydrocarbon interior of a membrane and proteins only associated with the (inner or outer) surface of the membrane. A number of characteristic features of start and stop signals are discussed in the chapter along with some interpretations of their possible functional relevance.