7.3 Targeting Cell Membrane Structures: Protein Component
The other major structural features of cell membranes are the proteins. A large number of
protein molecules are embedded in the lipid bilayer to a greater or lesser extent. Some are
anchored only superficially onto an outer or inner monolayer, but there are also some span-
ning the entire width of the membrane (transmembrane proteins). Structurally, the mem-
brane proteins include (1) simple helical proteins,like glycophorinof red blood cells; and
(2)globulins,like the complex multisubunit ionophores (e.g., the cholinoceptors; see
section 4.2). They are anchored in the hydrophobic interior of the bilayer by stretches of
apolar amino acids that form hydrophobic bonds with the lipid hydrocarbon chains, but
their hydrophilic parts protrude into the outer and inner aqueous phase and serve as the
major communication link between cells. Most proteins carry oligosaccharides on their
outer surfaces and are therefore called glycoproteins; the oligosaccharide “antennae” often
serve as a recognition structure—for example, erythrocyte blood type factors.
Functionally, the membrane proteins can be divided into three broad categories:
- Transmembrane ion channel proteins
Voltage-gated ion channel proteins (e.g., Na+channel, K+channel, Ca^2 +channel)
Ligand-gated ion channel proteins (e.g., GABA-A receptor)
Gap-junction channels - Signal transduction proteins
G-protein coupled receptors (e.g., adenylate cyclase system, phospholipase
C system) - Transport proteins
Energy-dependent pumps (e.g., Na+,K+-ATPase)
Carrier proteins (e.g., large neutral amino acid transporter, Na+/glucose-cotransport
protein)
The voltage-gated ion channel proteins (VGICs) are protein pores that regulate and
permit the passage of ions from the extracellular environment to the intracellular milieu or
vice versa. Conformational changes in the shape of the protein permit the ion transport
process to be regulated. In VGICs, these conformational changes are driven by alter-
ations in the transmembrane voltage gradient. In ligand-gated ion channels (LGICs), the
conformational changes occur following binding of a small molecule to the LGIC pro-
tein. Neurotransmitters are typical ligands that bind to such a protein. The GABA-A
receptor is a classic example of such a protein.
Gap junction channels represent protein assemblies that are central to the process of
electrical transmission between neurons. Classically, information exchange between
neurons was described as occurring via chemical transmission, involving the diffusion of
a neurotransmitter molecule from one neuron to the next, a process described in detail in
chapter 4. In comparison to chemical transmission, electrical transmission is much sim-
pler. In response to electrochemical gradients, ions simply flow from a stimulated presy-
naptic cell through the gap junction channels that directly connect the cytoplasm of one
cell to the cytoplasm of a second adjacent cell, thus changing the electrical activity
within the postsynaptic cell. A gap junction is an aggregate of gap junction channels. A
gap junction channel is made from two mirror-image symmetrical components called
412 MEDICINAL CHEMISTRY