The ability to carry out vectorial transport is crucial for the functioning of several organ systems, such as the gastrointestinal tract and kidneys. Lipid rafts, which contain lipids like sphingomyelin and cholesterol, are present in certain regions of the membrane and often associate with specific proteins. These lipid rafts have various functions, including the segregation of signaling molecules.

Proteins make up approximately 50% of the plasma membrane and are classified as integral, lipid-anchored, or peripheral. Integral membrane proteins are embedded in the lipid bilayer, with hydrophobic amino acid residues associated with the hydrophobic fatty acyl chains of the membrane lipids. Many of these proteins span the bilayer, referred to as transmembrane proteins. Transmembrane proteins have hydrophobic and hydrophilic regions, with the hydrophobic region typically in the form of an α helix. The hydrophilic amino acid residues are exposed to the aqueous environment on either side of the membrane. Some transmembrane proteins traverse the membrane multiple times.

There is a superfamily of membrane proteins that serve as receptors for hormones, neurotransmitters, and numerous drugs. These receptors are known as G protein–coupled receptors and are coupled to heterotrimeric G proteins. They span the membrane with seven α-helical domains. The ligand binding site for each ligand is either on the extracellular portion of the protein (large ligands) or in the membrane-spanning portion (small ligands), while the cytoplasmic portion binds to the G protein. This superfamily of membrane proteins is the third largest family of genes in humans, and almost half of all nonantibiotic prescription drugs target G protein–coupled receptors.

Proteins can also be attached to the membrane through lipid anchors. The protein is covalently attached to a lipid molecule, which is then embedded in one leaflet of the bilayer. Glycosylphosphatidylinositol (GPI) anchors proteins to the outer leaflet of the membrane. Proteins can be attached to the inner leaflet via their amino-terminus by fatty acids (e.g., myristate or palmitate) or via their carboxyl-terminus by prenyl anchors (e.g., farnesyl or geranylgeranyl).

Peripheral proteins may be associated with the polar head groups of the membrane lipids, but they more commonly bind to integral or lipid-anchored proteins.

In many cells, the outer leaflet lipids and many of the proteins on the outer surface of the membrane are glycosylated, meaning they have attached short chains of sugars called oligosaccharides. These glycolipids and glycoproteins collectively form the glycocalyx. Depending on the cell, these glycolipids and glycoproteins may be involved in cell recognition (e.g., cell surface antigens) and the formation of cell-cell interactions (e.g., attachment of neutrophils to vascular endothelial cells).

While plasma membrane proteins perform various important cellular functions, the focus of this chapter is on one group of plasma membrane proteins: the membrane transport proteins, also known as transporters. It has been estimated that approximately 10% of human genes (around 2000) code for transporters, which are also targets for numerous drugs.
CHAPTER 1 Principles of Cell and Membrane Function out vectorial transport of substances from one side of the epithelium to the opposite side. The ability to carry out vectorial transport is crucial for the functioning of several organ systems (e.g., the gastrointestinal tract and kidneys). In addition, some regions of the membrane contain lipids (e.g., sphingomyelin and cholesterol) that aggregate into what are called lipid rafts. These lipid rafts often have an association with specific proteins, which diffuse in the plane of the membrane as a discrete unit. Lipid rafts appear to serve a number of functions. One important function of these rafts is to segregate signaling molecules.
As much as 50% of the plasma membrane is composed of proteins. These membrane proteins are classified as integral, lipid-anchored, or peripheral.
Integral membrane proteins are imbedded in the lipid bilayer, where hydrophobic amino acid residues are associated with the hydrophobic fatty acyl chains of the membrane lipids. Many integral membrane proteins span the bilayer; such proteins are termed transmembrane proteins. Transmembrane proteins have both hydrophobic and hydrophilic regions. The hydrophobic region, often in the form of an α helix, spans the membrane. Hydrophilic amino acid residues are then exposed to the aqueous environment on either side of the membrane. Transmembrane proteins may pass through the membrane multiple times.
Thereisasuperfamilyofmembraneproteinsthatserveasreceptorsformanyhormones,neurotransmitters,andnumerousdrugs.ThesereceptorsarecoupledtoheterotrimericGproteinsandaretermedG protein–coupled receptors (see ).Theseproteinsspanthemembranewithsevenα-helicaldomains.Thebindingsiteofeachligandiseitherontheextracellularportionoftheprotein(largeligands)orinthemembrane-spanningportion(smallligands),whereasthecytoplasmicportionbindstotheGprotein.Thissuperfamilyofmembraneproteinsmakesupthethirdlargestfamilyofgenesinhumans.NearlyhalfofallnonantibioticprescriptiondrugsaretargetedtowardGprotein–coupledreceptors.
A protein can also be attached to the membrane via lipid anchors. The protein is covalently attached to a lipid molecule, which is then embedded in one leaflet of the bilayer. Glycosylphosphatidylinositol (GPI) anchors proteins to the outer leaflet of the membrane. Proteins can be attached to the inner leaflet via their amino-terminus by fatty acids (e.g., myristate or palmitate) or via their carboxyl-terminus by prenyl anchors (e.g., farnesyl or geranylgeranyl).
Peripheral proteins may be associated with the polar head groups of the membrane lipids, but they more commonly bind to integral or lipid-anchored proteins.
In many cells, some of the outer leaflet lipids, as well as many of the proteins exposed on the outer surface of the membrane, are glycosylated (i.e., have short chains of sugars, called oligosaccharides, attached to them). Collectively, these glycolipids and glycoproteins form what is called the glycocalyx. Depending on the cell these glycolipids and glycoproteins may be involved in cell recognition (e.g., cell surface antigens) and formation of cell-cell interactions (e.g., attachment of neutrophils to vascular endothelial cells).
Although plasma membrane proteins perform many important cellular functions, as noted previously, the remainder of this chapter focuses on one group of plasma membrane proteins: the membrane transport proteins, or transporters. It has been estimated that approximately 10% of human genes (≈2000) code for transporters. They are also targets for numerous drugs.