A transmembrane receptor is a biological receptor (a protein) that passes at least once through a biological membrane (so-called integral membrane proteins). This can be the plasma membrane of a cell, or a membrane of an organelle in eukaryotes. Transmembrane receptors are used to recognize a specific signal on one side of the membrane, then relaying it through the membreane, without the original signal itself having to pass through the membrane. They play an important role in signal transduction. Many transmembrane receptors are dimers or oligomers, or become such once activated. A transmembrane receptor usually consists of three parts or domains.
E=extracellular space; I=intracellular space; P=plasma membrane (image in the PD)
The extracellular domain
The extracellular domain is the part of the receptor that sticks out of the membrane on the outside of the cell or organelle. If the receptor passes through the membrane several times, the external domain can be comprised of several loops sticking out of the membrane, usually connected by disulfide bonds. Its main function is to recognize a very specific signal, for example, a molecule (like a hormone) or a change in membrane potential, that is, the difference of the electrical charge on both sides of the membrane. Additionally, the extracellular domain can be subject to glycosylation(???). Finally, it can bind to other integral membrane proteins or extracellular proteins by protein-protein-interactions or disulfide bonds.
The transmembrane domain
For each time the receptor passes through the membrane, a part of the receptor has to be embedded into the membrane. Usually, the 20-25 amino acids that make up these parts of the receptor are hydropobic like the membrane itself. Surrounding these parts, there are usually a few hydrophilic amino acids that match the heads of the lipids the membrane is made of; also, they prevent the following amino acids from slipping into the membrane as well, pushing the receptor out of the membrane. This typical property of transmembrane domains is used in hydropathy plots, determining wether newly found proteins are transmembrane proteins by their amino acid sequence alone. Most transmembrane domains are thought to be α helices, but β sheets have been found as well. Some transmembrane domains can open an ion channel on activation of the extracellular domain; their sequence can contain hydrophilic amino acids, that are facing each other when the channel is open, so soluble ions can pass through. The other transmembrane domains undergo a structural change upon activation of the extracellular domain, relaying the signal to the intracellular domain.
The intracellular domain
The intracellular (or cytoplasmic) domain of the receptor interacts with the interior of the cell or organelle, relaying the signal. There are two fundamentally different ways for this interaction:
- The intracellular domain communicates via specific protein-protein-interactions with effector proteins, which in turn send the signal along a signal chain to its destination.
- The intracellular domain has enzymatic activity. Often, this is a tyrosine kinase activity. The enzymatic activity can also be located on an enzyme associated with the intracellular domain.
Regulation of receptor activity
There are several ways for the cell to regulate the activity of a transmembrane receptor. Most of them work through the intracellular domain. The most important ways are phosphorylation and internalization (see ubiquitin).