Transmembrane Protein

The membrane of a cell is not only a border; it is also an interface. The most critical molecules involved in interface functioning are proteins that are embedded within the membrane. Many of these proteins span the distance from the outside to the inside of the cell (in part because they are much larger than the lipids that make up the membrane) and are referred to as transmembrane proteins. Transmembrane proteins are a class of integral proteins (i.e., proteins that penetrate into or through the membrane bilayer).

The lipid molecules of the membrane bilayer are predominantly hydrophobic (i.e., they do not interact strongly with polar water molecules). The portion of the transmembrane protein that is embedded in the bilayer must therefore have residues that are not polar. Commonly, these residues form a coil, or helix , that is hydrophobic and therefore stable within the bilayer.

Transmembrane proteins have three regions or domains that can be defined: the domain in the bilayer, the domain outside the cell (called the extracellular domain), and the domain inside the cell (called the intercellular domain). Even though a cell membrane is somewhat fluid, the orientation of transmembrane proteins does not change. The proteins are so large that the rate for them to change orientation is extremely small. Thus, the extracellular part of the transmembrane protein is always outside the cell and the intercellular portion is always inside.

Transmembrane proteins play several roles in the functioning of cells. Communication is one of the most important roles: The proteins are useful for signaling to the cell what the external environment contains. Receptors are capable of interacting with specific substrate molecules on the extracellular domain. Once a protein binds to substrate, a change in the geometry near the binding site results in subsequent changes in the structure of the intercellular domain. These changes result in a cascade effect—another protein in the cell changes, affecting the next protein, and so on. Thus, transmembrane proteins are capable of initiating signals that are responsive to the external environment of the cell but ultimately lead to actions that take place in other structures of the cell.

In addition to serving as a way for the cell to gather information about the external environment, transmembrane proteins are associated with controlling the exchange of materials across the membrane. The proteins most involved in this process are called porins. These molecules appear in clusters that create pores (or channels) within the membrane. In many cases the pores are controlled (or regulated) by other proteins so that they are open under some circumstances and closed under others.

Nerve cell signaling provides a good example of this functionality. Nerve cells propagate electrical signals called action potentials by using the flow of ions across the membrane. The channels that allow the flow of ions are usually closed in their resting state but open when a signal occurs. These proteins form voltage-gated channels. When one nerve cell interacts with another, a different mechanism opens the channels. In this case, a receptor protein binds a neurotransmitter; this interaction affects the channel proteins so that they are opened for ion flow. This structure is referred to as a ligand-gated channel. The ligand is the neurotransmitter in this case, but other ligand-gated channels also exist and all use transmembrane proteins.

see also Proteins; Neurotransmitters.

Thomas A. Holme

Bibliography

Branden, C., and Tooze, J. (1991). Introduction to Protein Structure. New York: Garland Publishing.

Voet, D., and Voet, J. G. (1995). Biochemistry. New York: Wiley.