Membrane or Transmembrane receptors are specialized integral membrane proteins that take part in communication between the the cell and the outside world. Extracellular signaling molecules (usually hormones, neurotransmitters, cytokines, growth factors or cell recognition molecules) attach to the receptor, triggering changes in the function of the cell. This process is called signal transduction: The binding initiates a chemical change on the intracellular side of the membrane. In this way the receptors play a unique and important role in cellular communications and signal transduction.
structure of membrane receptors:
Like any integral membrane protein, a transmembrane receptor may be subdivided into three parts or domains.
[edit] 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 potential), and in many receptors these ligands bind to the extracellular domain.
[edit] Transmembrane domain
Main article: Transmembrane domain
In the majority of receptors for which structural evidence exists, transmembrane alpha helices make up most of the transmembrane domain. In certain receptors, such as the nicotinic acetylcholine receptor, the transmembrane domain forms a protein-lined pore through the membrane, or ion channel. 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 bacteriorhodopsin, the detailed structure of which has been determined by crystallography).
[edit] 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.
* With enzyme-linked receptors, 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.
Based on structural and functional similarities, membrane receptors are mainly divided into 3 classes: The ion channel-linked receptor; The enzyme-linked receptor and G protein-coupled receptor.
* Ion channel-linked receptors are ion-channels (including cation-channels and anion-channels) themselves and constitute a large family of multipass transmembrane proteins. They are involved in rapid signaling events most generally found in electrically excitable cells such as neurons and are also called ligand-gated ion channels. Opening and closing of Ion channels are controlled by neurotransmitters.
* Enzyme-linked receptors are either enzymes themselves, or are directly associated with the enzymes that they activate. These are usually single-pass transmembrane receptors, with the enzymatic portion of the receptor being intracellular. The majority of enzyme-lined receptors are protein kinases, or associate with protein kinases.
* G protein-coupled receptors are integral membrane proteins that possess seven membrane-spanning domains or transmembrane helices. These receptors activate a G protein ligand binding. G-protein is a trimeric protein. The 3 subunits are called α、β and γ. The α subunit can bind with guanosine diphosphate, GDP. This causes phosphorylation of the GDP to guanosine triphosphate, GTP, and activates the α subunit, which then dissociates from the β and γ subunits. The activated α subunit can further affect intracellular signaling proteins or target functional proteins directly.
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