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Encyclopedia > Receptor (biochemistry)

In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. Ligand-induced changes in the behavior of receptor proteins result in physiological changes that constitute the biological actions of the ligands. Biochemistry is the study of the chemical processes and transformations in living organisms. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... // The cell membrane (also called the plasma membrane or plasmalemma) is a semipermeable lipid bilayer common to all living cells. ... Organelles. ... The eukaryotic cell nucleus. ... It has been suggested that this article or section be merged with ligand. ... Chemical structure of D-Aspartic Acid, a common Amino Acid neurotransmitter. ... Norepinephrine A hormone (from Greek όρμή - to set in motion) is a chemical messenger from one cell (or group of cells) to another. ...

Contents

Binding and activation

Ligand binding to a receptor is an equilibrium process: Ligands bind to an empty receptor and they dissociate from it (according to the law of mass action): Chemical equilibrium is the state in which the concentrations of the reactants and products have no net change over time. ... Mass action in science is the idea that a large number of small units (especially atoms or molecules) acting randomly by themselves can in fact have a larger pattern. ...

left [ Ligand right ] cdot left [ Receptor right ] overset{ K_d}{ rightleftharpoons } left [ Ligand-receptor complex right ]
(the brackets stand for concentrations)

A measure of how well a certain molecule fits into a given receptor is the binding affinity which is measured as the dissociation constant Kd (good fit means high affinity and a low Kd). The activation of the second messenger cascade and the final biological response is achieved only when at a certain time point a significant number of receptors are activated by bound ligands. In chemistry and biochemistry, a dissociation constant or an ionization constant is a specific type of equilibrium constant used for reversible reactions or processes. ... In cell physiology, a secondary messenger system (also known as a second messenger system) is a method of cellular signalling where the signalling molecule does not enter the cell, but rather utilizes a cascade of events that transduces the signal into a cellular change. ...


Agonists versus antagonists

Not every ligand that binds to a receptor also activates the receptor. The following classes of ligands exist:

  • (Full) agonists are able to activate the receptor and result in a maximal biological response. Most natural ligands are full agonists
  • Partial agonists are not able to activate the receptor maximally, resulting in a partial biological response compared to a full agonist.
  • Antagonists bind to the receptor but do not activate it. This results in a receptor blockade that inhibits the binding of agonists.
  • Inverse agonists are antagonists that are able to further reduce the receptor activation by decreasing its basal activity

Overview

Transmembrane receptor:E=extracellular space; I=intracellular space; P=plasma membrane
Transmembrane receptor:E=extracellular space; I=intracellular space; P=plasma membrane

Receptors exist in different types, dependent on their ligand and function: from meta; yet another one of my own drawings;-) File links The following pages link to this file: Transmembrane receptor Receptor (biochemistry) Categories: GFDL images ... from meta; yet another one of my own drawings;-) File links The following pages link to this file: Transmembrane receptor Receptor (biochemistry) Categories: GFDL images ... It has been suggested that this article or section be merged with ligand. ...

Peripheral membrane proteins are proteins that adhere only temporarily to the biological membrane with which they are associated. ... A hormone receptor is a receptor protein on the surface of a cell that binds to a specific hormone. ... Transmembrane receptors are integral membrane proteins, which reside and operate typically within a cells plasma membrane, but also in the membranes of some subcellular compartments and organelles. ... Transmembrane receptors are integral membrane proteins, which reside and operate typically within a cells plasma membrane, but also in the membranes of some subcellular compartments and organelles. ... A diagonal molecular slab from the DPPC lipid bilayer simulation1; color scheme: PO4 - green, N(CH3)3 - violet, water - blue, terminal CH3 - yellow, O - red, glycol C - brown, chain C - grey. ... // The cell membrane (also called the plasma membrane or plasmalemma) is a semipermeable lipid bilayer common to all living cells. ... This article or section does not cite its references or sources. ... It has been suggested that this article or section be merged with ligand. ... Based on their structural and functional characteristics, neurotransmitter receptors can be classified into two broad categories: metabotropic and ionotropic receptors. ... G-proteins, short for guanine nucleotide binding proteins, are a family of proteins involved in second messenger cascades. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... Ion channels are pore-forming proteins that help to establish and control the small voltage gradient that exists across the plasma membrane of all living cells (see cell potential) by allowing the flow of ions down their electrochemical gradient. ... Ionotropic receptor (also ligand gated ion channel) are a subclass of transmembrane receptors. ... In cell biology, molecular biology and related fields, the word intracellular means inside the cell. It is used in contrast to extracellular (outside the cell). ... Steroid skeleton of lanosterol. ... The eukaryotic cell nucleus. ... Gene expression, or simply expression, is the process by which a genes DNA sequence is converted into the structures and functions of a cell. ... X-ray crystallography or single-crystal X-ray diffraction is an analytical technique which uses the diffraction pattern produced by bombarding a single crystal with X-rays to solve the crystal structure. ... The action of drugs on the human body is called pharmacodynamics, and what the body does with the drug is called pharmacokinetics. ...

Peripheral membrane protein receptors

Peripheral membrane proteins are proteins that adhere only temporarily to the biological membrane with which they are associated. These molecules attach to integral membrane proteins, or penetrate the peripheral regions of the lipid bilayer. The regulatory protein subunits of many ion channels and transmembrane receptors, for example, may be defined as peripheral membrane proteins. In contrast to integral membrane proteins, peripheral membrane proteins tend to collect in the water-soluble component, or fraction, of all the proteins extracted during a protein purification procedure. Proteins with GPI anchors are an exception to this rule and can have purification properties similar to those of integral membrane proteins.


The reversible attachment of proteins to biological membranes has been shown to regulate cell signaling and many other important cellular events, through a variety of mechanisms.[1] For example, the close association between many enzymes and biological membranes may bring them into close proximity with their lipid substrate(s).[2] Membrane binding may also promote rearrangement, dissociation, or conformational changes within many protein structural domains, resulting in an activation of their biological activity.[3][4] Additionally, the positioning of many proteins are localized to either the inner or outer surfaces or leaflets of their resident membrane.[5] This facilitates the assembly of multi-protein complexes by increasing the probability of any appropriate protein-protein interactions


Transmembrane receptors

Transmembrane receptors are integral membrane proteins, which reside and operate typically within a cell's plasma membrane, but also in the membranes of some subcellular compartments and organelles. Binding to a signalling molecule or sometimes to a pair of such molecules on one side of the membrane, transmembrane receptors initiate a response on the other side. In this way they play a unique and important role in cellular communications and signal transduction. Transmembrane receptors are integral membrane proteins, which reside and operate typically within a cells plasma membrane, but also in the membranes of some subcellular compartments and organelles. ...


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 G-protein coupled receptors).


1 Domains 1.1 The extracellular domain 1.2 The transmembrane domain 1.3 The intracellular domain 2 Regulation of receptor activity 3 Examples of transmembrane receptors 4 See also 5 External links


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



E=extracellular space; I=intracellular space; P=plasma membrane



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 potential), and in many receptors these ligands bind to the extracellular domain.



The 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).



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. 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.


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).



Examples of transmembrane receptors G-protein coupled receptors - Adrenergic receptor, Olfactory receptors, Receptor tyrosine kinases - Epidermal growth factor receptor, Insulin Receptor, Fibroblast growth factor receptors, High affinity neurotrophin receptors, and Eph Receptors Integrins Low Affinity Nerve Growth Factor Receptor NMDA receptor Toll-like receptor T cell receptor CD28


Metabotropic receptors

Based on their structural and functional characteristics, neurotransmitter receptors can be classified into two broad categories: metabotropic and ionotropic receptors. In contrast to the latter, metabotropic receptors do not form an ion channel pore; rather, they are indirectly linked with ion-channels on the plasma membrane of the cell through signal transduction mechanisms. This class of receptors includes the metabotropic glutamate receptors, muscarinic acetylcholine receptors, GABAB receptors, and most serotonin receptors, as well as receptors for norepinephrine, epinephrine, histamine, dopamine, neuropeptides (Austin, 2004; Purves et al., 2001) and endocannabinoids.


All metabotropic receptors are monomeric proteins with seven transmembrane domains. The protein's N terminus is on the extracellular side of the membrane and its C terminus is on the intracellular side (Purves et al., 2001).


Metabotropic receptors have neurotransmitters as ligands, which, when bound to the receptors, initiate cascades that can lead to channel-opening or other cellular effects. When a ligand, also called the primary messenger, binds to the receptor, or the transducer, the latter activates a primary effector, which can go on to activate secondary messengers or have other effects. Since opening channels by metabotropic receptors involves activating a number of molecules in turn, channels associated with these receptors take longer to open than ionotropic receptors do, and they are thus not involved in mechanisms that require quick responses (Kandel et al., 2000, p. 240). However, metabotropic receptors also remain open from seconds to minutes (Kandel et al., 2000, p. 250-251). Thus they have a much longer-lasting effect than ionotropic receptors, which open quickly but only remain open for a few milliseconds (Austin, 2004). While ionotropic channels have an effect only in the immediate region of the receptor, the effects of metabotropic receptors can be more widespread through the cell.


Metabotropic receptors can both open and close channels. They can make a membrane more excitable by closing K+ channels, retaining positive charge within the cell and thus reducing the amount of current necessary to cause an action potential (Kandel et al., 2000, p. 242-243). Metabotropic receptors on the presynaptic membrane can inhibit or, more rarely, facilitate neurotransmitter release from the presynaptic neuron (Schmitz et al., 2001). These receptors can be further classified into receptor tyrosine kinases and G-protein-coupled receptors, or GPCRs (Kandel et al., 2000, p. 229).


G protein-coupled receptors

These receptors are also known as seven transmembrane receptors or 7TM receptors. Figure 1. ...

Amanita muscaria from which muscarine was isolated Acetylcholine - natural agonist of muscarinic and nicotinic receptors. ... An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of the neurotransmitter acetylcholine. ... The chemical compound acetylcholine, often abbreviated as ACh, was the first neurotransmitter to be identified. ... Muscarine, L-(+)-muscarine, or muscarin is a natural product found in certain mushrooms, particularly in Inocybe and Clitocybe species. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... Adenosine is a nucleoside comprised of adenine attached to a ribose (ribofuranose) moiety via a β-N9-glycosidic bond. ... The adrenergic receptors (or adrenoceptors) are a class of G_protein coupled receptors that is the target of catecholamines. ... Epinephrine Norepinephrine The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of the catecholamines. ... Epinephrine (INN) or adrenaline (BAN) is a hormone and a neurotransmitter. ... Norepinephrine A hormone (from Greek όρμή - to set in motion) is a chemical messenger from one cell (or group of cells) to another. ... Oral medication A medication is any drug taken to cure or reduce the symptoms of an illness or ongoing medical condition. ... The GABA receptors are a group of receptors with γ-aminobutyric acid (GABA) as their endogenous ligand. ... Gamma-aminobutyric acid (usually abbreviated to GABA) is an inhibitory neurotransmitter found in the nervous systems of widely divergent species. ... The angiotensin receptors are a class of G protein-coupled receptors with angiotensins as ligands. ... Angiotensin is an oligopeptide in the blood that causes vasoconstriction, increased blood pressure, and release of aldosterone from the adrenal cortex. ... The cannabinoid receptors are a class of receptors under the G-protein coupled receptor superfamily. ... Cannabinoids are a group of chemicals which activate the bodys cannabinoid receptors. ... Cholecystokinin receptors or CCK receptors are a group of G_protein coupled receptors. ... Cholecystokinin (from Greek chole, bile; cysto, sac; kinin, move; hence, move the bile-sac (gall bladder)) is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein. ... The dopamine receptors are a class of metabotropic G-protein-coupled receptors with the neurotransmitter dopamine as their endogenous ligand. ... Dopamine is a phenethylamine naturally produced by the human body. ... The glucagon receptor is a 62 kDa peptide that is activated by glucagon and is a member if the g-protein coupled family of receptors. ... Glucagon ball and stick model A microscopic image stained for glucagon. ... Metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor which are active through an indirect metabotropic process. ... Glutamate is the anion of glutamic acid. ... The histamine receptors are a class of G-protein coupled receptors with histamine as their endogenous ligand. ... This article or section does not cite any references or sources. ... Olfactory receptors are a type of G protein-coupled receptor in olfactory receptor neurons. ... Young boy smelling a flower Olfaction, which is also known as Olfactics is the sense of smell, and the detection of chemicals dissolved in air. ... To meet Wikipedias quality standards, this article may require cleanup. ... An opioid is a chemical substance that has a morphine-like action in the body. ... A rhodopsin molecule (yellow) with bound retinal (orange), embedded in a cell membrane (lipids shown as green, head groups as red/blue). ... A photoreceptor, or photoreceptor cell, is a specialized type of neuron found in the eyes retina that is capable of phototransduction. ... The secretin receptor is a G protein-coupled receptor which binds secretin. ... Secretin is a peptide hormone produced in the S cells of the duodenum. ... In the field of neurochemistry, 5-HT receptors are receptors for the neurotransmitter and peripheral signal mediator serotonin, also known as 5-hydroxytryptamine or 5-HT. 5-HT receptors are located on the cell membrane of nerve cells and other cell types in animals and mediate the effects of serotonin... Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system (CNS) and enterochromaffin cells in the gastrointestinal tract of animals including humans. ... There are five known somatostatin receptors, SSTR1-5. ... Somatostatin is a hormone. ... General Name, Symbol, Number calcium, Ca, 20 Chemical series alkaline earth metals Group, Period, Block 2, 4, s Appearance silvery white Standard atomic weight 40. ... Typical structure of a chemokine receptor, with seven transmembrane domains and a characteristic DRY motif in the second intracellular domain. ... Chemokines are a class of chemotactic cytokines, or small secreted protein signals. ...

Receptor Tyrosine Kinases

These receptors detect ligands and propagate signals via the tyrosine kinase of their intracellular domains. This family of receptors includes; Tyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation A tyrosine kinase (EC 2. ...

The erythropoietin receptor is a 66 kda peptide and is a member of the cytokine receptor family. ... Erythropoietin (IPA pronunciation: , alternative pronunciations: ) or EPO is a glycoprotein hormone that is a cytokine for erythrocyte (red blood cell) precursors in the bone marrow. ... In molecular biology, the insulin receptor is a transmembrane receptor that is activated by insulin. ... Insulin (from Latin insula, island, as it is produced in the Islets of Langerhans in the pancreas) is a polypeptide hormone that regulates carbohydrate metabolism. ... The largest sub-family of Receptor Tyrosine Kinases is the Eph family, comprised of 16 known receptors (14 found in mammals) with 9 known ephrin ligands (8 found in mammals). ... The Insulin-like Growth Factor 1 (IGF-1) Receptor is a transmembrane receptor that is activated by IGF-1 and by the related growth factor IGF-II. It belongs to the large class of tyrosine kinase receptors. ... Growth factor is a protein that acts as a signaling molecule between cells (like cytokines and hormones) that attaches to specific receptors on the surface of a target cell and promotes differentiation and maturation of these cells. ... Cytokines are a group of proteins and peptides that are used in organisms as signaling compounds. ...

Guanylyl cyclase receptors

Atrial natriuretic factor (ANF), or atrial natriuretic peptide (ANP), is a peptide hormone that is released by walls of the cardiac atrium in response to high NaCl concentration, high extracellular fluid volume, or high blood volume. ... Guanylin is a 15 amino acid peptide that is secreted by goblet cells in the colon. ...

Ionotropic receptors

The entire repertoire of human plasma membrane receptors is listed at the Human Plasma Membrane Receptome (http://receptome.stanford.edu). Nicotinic acetylcholine receptors, or nAChRs, are ionotropic receptors that form ion channels in cells plasma membranes. ... An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of the neurotransmitter acetylcholine. ... The chemical compound acetylcholine, often abbreviated as ACh, was the first neurotransmitter to be identified. ... Articles with similar titles include Niacin, which is the nicotinic acid, and has a very different biological effect. ... The Glycine receptor is one of the most widely distributed inhibitory receptors in the Central nervous system. ... For the plant, see Glycine (plant). ... Strychnine (pronounced (British) or (U.S.)) is a very toxic (LD50 = 10 mg approx. ... The GABA receptors are a group of receptors with γ-aminobutyric acid (GABA) as their endogenous ligand. ... Gaba may refer to: Gabâ or gabaa (Philippines), the concept of negative karma of the Cebuano people GABA, the gamma-amino-butyric acid neurotransmitter GABA receptor, in biology, receptors with GABA as their endogenous ligand Gaba 1 to 1, an English conversational school in Japan Marianne Gaba, a US model... Glutamate is a neurotransmitter in nerve cells which binds to all glutamate receptors located on neuron membranes, and is an example of a transmembrane receptor. ... The NMDA receptor (NMDAR) is an ionotropic receptor for glutamate (NMDA (N-methyl d-aspartate) is a name of its selective specific agonist). ... The α-amino-3-hydroxy-5-methylisoxazole-4- propionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system (CNS). ... Kainate receptors are ionotropic receptors which respond to both glutamate, which is their physiological ligand, or kainate which is a drug first isolated from red alga Digenea simplex. ... Glutamate is the anion of glutamic acid. ... In the field of neurochemistry, 5-HT receptors are receptors for the neurotransmitter and peripheral signal mediator serotonin, also known as 5-hydroxytryptamine or 5-HT. 5-HT receptors are located on the cell membrane of nerve cells and other cell types in animals and mediate the effects of serotonin... Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system (CNS) and enterochromaffin cells in the gastrointestinal tract of animals including humans. ...


Intracellular receptors

Transcription factors

Nuclear receptors are a class of intracellular receptors which function as ligand activated transcription factors which up or down regulate the expression of genes. ... Steroid hormone receptors are generally intracellular (specifically cytoplasmatic) receptors that perform signal transduction for steroid hormones. ...

Various

The sigma-1 receptor is a transmembrane protein expressed in many different tissue types. ... Apart from exerting effects on the genome via intracellular steroid receptors, neuroactive steroids (or neurosteroids) rapidly alter neuronal excitability through interaction with neurotransmitter-gated ion channels. ... Inositol triphosphate receptor (IP3R) is a membrane glycoprotein complex acting as Ca2+ channel activated by inositol triphosphate (IP3). ... Inositol triphosphate or inositol 1,4,5-triphosphate (also commonly known as triphosphoinositol; abbreviated InsP3 or IP3), together with diacylglycerol, is a second messenger molecule used in signal transduction in biological cells. ...

Role in Genetic Disorders

Many genetic disorders involve hereditary defects in receptor genes. Often, it is hard to determine whether the receptor is nonfunctional or the hormone is produced at decreased level; this gives rise to the "pseudo-hypo-" group of endocrine disorders, where there appears to be a decreased hormonal level while in fact it is the receptor that is not responding sufficiently to the hormone. A genetic disorder or a clinical phenotype. ... Norepinephrine A hormone (from Greek όρμή - to set in motion) is a chemical messenger from one cell (or group of cells) to another. ... Endocrinology is a branch of medicine dealing with disorders of the endocrine system and its specific secretions called hormones. ...


Receptor Regulation

Cells can increase (upregulate) or decrease (downregulate) the number of receptors to a given hormone or neurotransmitter to alter its sensitivity to this molecule. This is a locally acting feedback mechanism. Upregulation is the process by which a cell increases the number of receptors to a given hormone or neurotransmitter to improve its sensitivity to this molecule. ... Downregulation is the process by which a cell decreases the number of receptors to a given hormone or neurotransmitter to reduce its sensitivity to this molecule. ... Norepinephrine A hormone (from Greek όρμή - to set in motion) is a chemical messenger from one cell (or group of cells) to another. ... Chemical structure of D-Aspartic Acid, a common Amino Acid neurotransmitter. ... It has been suggested that this article or section be merged with Feedback loop. ...


See also

This article or section does not cite its references or sources. ... Technical advancements in recent years have allowed progress toward the understanding of the brain and how drugs can be made to affect it. ... This article or section is in need of attention from an expert on the subject. ... The Ki Database (or Ki DB) is a public domain database of published binding affinities (Ki) of drugs and chemical compounds for receptors, neurotransmitter transporters, ion channels, and enzymes. ...

External links

  • IUPHAR GPCR Database and Ion Channels Compendium
  • MeSH Cell+surface+receptors

  Results from FactBites:
 
Receptor (biochemistry) - Wikipedia, the free encyclopedia (386 words)
In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand.
Many hormone receptors and neurotransmitter receptors are transmembrane proteins: transmembrane receptors are embedded in the lipid bilayer of cell membranes, that allow the activation of signal transduction pathways in response to the activation by the binding molecule, or ligand.
Often, it is hard to determine whether the receptor is nonfunctional or the hormone is produced at decreased level; this gives rise to the "pseudo-hypo-" group of endocrine disorders, where there appears to be a decreased hormonal level while in fact it is the receptor that is not responding sufficiently to the hormone.
  More results at FactBites »

 
 

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