ABSTRACT
Cells and organelles within them are bounded by membranes, which are extremely thin (4.5 nm) films of lipids and protein molecules. The lipids form a bilayered sheet structure that is hydrophilic on its two outer surfaces and hydrophobic in between. Protein molecules are embedded in this layer, and in the simplest case they are arranged with three distinct regions: one hydrophobic transmembrane segment and two hydrophilic regions, one on each side of the membrane. Those proteins whose polypeptide chain traverses the membrane only once usually form functional globular domains on at least one side of the membrane (Figure 12.1a). Often these can be cleaved off by proteolytic enzymes. The hemagglutinin and neuraminidase of influenza virus (discussed in Chapter 5), G-proteins and receptors (discussed in Chapter 13), and HLA proteins (discussed in Chapter 15) are examples of such cleavage products that can be handled as functional soluble globular domains. The polypeptide chain of other transmembrane proteins passes through the membrane several times, usually as a helices but in some cases as b strands (Figure 12.1b,c). In these cases the hydrophilic regions on either side of the membrane are the termini of the chain and the loops between the membrane-spanning parts. Proteolytic cleavage of these hydrophilic regions produces a number of fragments, and function is not preserved. Some proteins do not traverse the membrane but are instead attached to one side either through a helices that lie parallel to the membrane surface (Figure 12.1d) or by fatty acids, covalently linked to the protein, that intercalate in the lipid bilayer of the membrane.
