The thermodynamic arguments discussed in the previous chapter make it clear that the TM segments of proteins will utilize secondary structure to satisfy the hydrogen bond needs of the peptide backbone. While a variety of combinations of secondary structures might be imagined in type III membrane proteins, all known protein structures cross the bilayer with either α-helices or β-strands, producing either helical bundles or β-barrels. This chapter looks at how understanding structure and function for a few proteins has provided the paradigms for these two known classes of integral membrane proteins.

HELICAL BUNDLES

Transmembrane (TM) α-helices have dominated the picture of membrane proteins, guided by early structural information on bacteriorhodopsin and by the first x-ray structure solved for membrane proteins, that of the photosynthetic reaction center (RC). The majority of integral membrane proteins whose high-resolution structures have been solved by x-ray crystallography exhibit the helical bundle motif (see examples in Chapters 9, 10, and 11). Helix–helix interactions have been analyzed in many of these, providing details of both tertiary and quaternary interactions. Identification of new integral membrane proteins in the proteome relies heavily on prediction of TM helices, as described in Chapter 6.

Bacteriorhodopsin

If a single protein dominated the thinking about structure, dynamics, and assembly of membrane proteins in the decades following 1970, that protein was bacteriorhodopsin (BR) from the purple membranes of the salt-loving bacterium Halobacter salinarum.