Transmembrane Receptor The Extracellular Domain The

Many transmembrane receptors are composed of two or more protein subunits which operate collectively and may dissociate when ligands bind, fall off, or at another stage of their "activation" cycles. They are often classified based on their molecular structure, or because the structure is unknown in any detail for all but a few receptors, based on their hypothesized (and sometimes experimentally verified) membrane topology. The polypeptide chains of the simplest are predicted to cross the lipid bilayer only once, while others cross as many as seven times (the so-called 7TM receptors that couple with G proteins).

Like any integral membrane protein, a transmembrane receptor may be subdivided into three parts or domains.

1 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 polypeptide chain of the receptor crosses the bilayer several times, the external domain can comprise several "loops" sticking out of the membrane. By definition. a receptor's main function is to recognize and respond to a specific ligand, for example, a neurotransmitter or hormone (although certain receptors respond also to changes in transmembrane potentialIn membrane biophysics sometimes used interchangeably with cell potential, but applicable to any lipid bilayer or membrane. Hence every organelle and every membranous compartment (such as a synthetic vesicle) has a transmembrane potential (although the si), and in many receptors these ligands bind to the extracellular domain.

2 The transmembrane domain

In the majority of receptors for which structural evidence exists, transmembrane alpha helicesWithin an integral membrane protein, a transmembrane helix is a segment that is alpha-helical in structure, roughly 20 amino acids in length and (though it may be presumed to lie within the protein, out of contact with the surrounding lipid bilayer) is sa make up most of the transmembrane domain. In certain receptors, such as the nicotinic acetylcholine receptorAn acetylcholine receptor (abbreviated AChR is an integral membrane protein that responds to the binding of the neurotransmitter acetylcholine by opening a pathway in the membrane for the diffusion of ions across the cell membrane. Classification Like oth, the transmembrane domain forms a protein-lined poreA pore in general, is some form of opening, usually very small. Pores can be found on many organisms, such as in plants, animals, and humans. More commonly, in talking about the skin, a pore is an opening that secretes sebaceous oil to lubricate and prote through the membrane, or ion channelIon channels are present in the membranes that surround all biological cells. By conducting and controlling the flow of ions, these pore-forming enzymes help establish the small negative voltage that all cells possess at rest (see cell potential). Basic f. Upon activation of an extracellular domain by binding of the appropriate ligand, the pore becomes accessible to ions, which then pass through. In other receptors, the transmembrane domains are presumed to undergo a conformational change upon binding, which exerts an effect intracellularly. In some receptors, such as members of the 7TM superfamily, the transmembrane domain may contain the ligand binding pocket (evidence for this and for much of what else is known about this class of receptors is based in part on studies of bacteriorhodopsinBacteriorhodopsin is a photosynthetic pigment used by archaea, most notably halobacteria. An integral membrane protein, it belongs to the " 7TM receptor family," so-called because each is composed of seven transmembrane alpha helices. The amino acid seque, the detailed structure of which has been determined by crystallography).

3 The intracellular domain

The intracellular (or cytoplasmicCytoplasm is the viscid, semifluid matter contained within the plasma membrane of a cell that helps to hold the cell together. In contrast to the protoplasm, however, the cytoplasm does not include the cell nucleus. The watery or aqueous component of the) 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 activityAn enzyme is a protein, or protein complex, that catalyzes a chemical reaction. Like any catalyst, enzymes work by lowering the activation energy of a reaction, thus allowing the reaction to proceed to its steady state or completion much faster than it ot. Often, this is a tyrosine kinase activity. The enzymatic activity can also be located on an enzyme associated with the intracellular domain.

4 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).

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