2. Receptors
• In biochemistry and pharmacology, a receptor is a protein molecule usually found embedded within the
plasma membrane surface of a cell that receives chemical signals from outside the cell.
What Are these Receptors And what do they do?
3. Receptor activation
how does an induced fit happen and what is the significance of the receptor changing shape?
messenger fits the binding site of the protein receptor it causes the binding site to change shape
5. Receptor activation
Fine balance involved in receptor, messenger binding
The bonding forces must be large enough to change the shape of the binding site, but not so strong that the
messenger is unable to leave
6.
7. Points to remember
Most receptors are membrane-bound proteins that contain an external binding site for
hormones or neurotransmitters. Binding results in an induced fi t that changes the receptor
conformation.
This triggers a series of events that ultimately results in a change in cellular chemistry.
Neurotransmitters and hormones do not undergo a reaction when they bind to receptors.
They depart the binding site unchanged once they have passed on their message.
The interactions that bind a chemical messenger to the binding site must be strong
enough to allow the chemical message to be received, but weak enough to allow the
messenger to depart.
10. Ion channel receptors
The structure of an ion channel. The bold lines show the hydrophilic sides of the channel.
11. Lock-gate mechanism for opening ion channels
Rapid response in millisecond
Synaptic transmission of signals between neurons usually involves ion channels.
Cationic ion channels Na+, K+, and Ca2+ ions.
Anionic ion channels Cl-
12. Structure of Ion channel
Nicotinic cholinergic receptor
Dextromethorphan Antitussive
Glycine receptor
Through Cl-
b-Alanine
Taurine
2-aminoethanesulfonic acid
Strychnine & Caffeine
13. Structure of Ion channel
Transverse view of Nicotinic cholinergic receptor, including transmembrane regions.
The subunits are arranged such that the second transmembrane region of each subunit faces the Central Pore Of The Ion
channel
17. Points to remember
Receptors controlling ion channels are an integral part of the ion channel. Binding of a messenger induces a
change in shape, which results in the rapid opening of the ion channel
Receptors controlling ion channels are called ligand-gated ion channel receptors. They consist
of five protein subunits with the receptor binding site being present on one or more of the
subunits.
Binding of a neurotransmitter to an ion channel receptor causes a conformational change in the
protein subunits such that the second transmembrane domain of each subunit rotates to open the
channel.
18. G-protein-coupled receptors
Activation of a G-protein-coupled receptor and G-protein
Response in Second
In general, GPCR activated by hormones (enkephalins and endorphin
) and slow-acting neurotransmitters (acetylcholine, dopamine, histamine, serotonin, glutamate, and noradrenaline)
19. Points to remember
Robert J. Lefkowitz
Howard Hughes Medical Institute and Duke University Medical Center, Durham, NC, USA
and
Brian K. Kobilka
Stanford University School of Medicine, Stanford, CA, USA
"for studies of G-protein–coupled receptors"
Today this family is referred to as G-protein–coupled receptors. About a thousand genes code for such receptors,
for example, for light, flavour, odour, adrenalin, histamine, dopamine and serotonin. About half of all medications
achieve their effect through G-protein– coupled receptors
2012 Nobel Prize in Chemistry
21. G-protein-coupled receptors
When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as
a guanine nucleotide exchange factor (GEF). The GPCR can then activate an associated G protein by exchanging
its bound GDP for a GTP.
Guanine nucleotide exchange factors (GEFs) activate monomeric GTPases by stimulating the release
of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP)
•Signal transduction at the intracellular domain
of transmembrane receptors, including recognition of
taste, smell and light.
•Protein biosynthesis (a.k.a. translation) at the ribosome.
•Control and differentiation during cell division.
•Translocation of proteins through membranes.
•Transport of vesicles within the cell. (GTPases control
assembly of vesicle coats.)
GTPase-Activating Proteins
22. G-protein-coupled receptors
Muscarinic acetylcholine receptors,
or mAChRs, are acetylcholine receptors that
form G protein-receptor complexes in the cell
membranes of certain neurons[1] and other cells
M1- to M5
M1 - secretion from salivary glands and stomach
M2 - slow heart rate
M3 - vasodilation
M4 - decreased locomotion
M5 - central nervous system
Atropine - an antagonist.Carbachol
23. G-protein-coupled receptors
The adrenergic receptors (or adrenoceptors) are a class of G protein-coupled receptors that are targets of
the catecholamines, especially norepinephrine(noradrenaline) and epinephrine (adrenaline).
Epinephrine Norepinephrine
Alfuzosin is a alpha-1 blocker class. As an antagonist of
the alpha-1 adrenergic receptor, it works by relaxing the
muscles in the prostate and bladder neck, making it easier
to urinate. It is thus used to treat benign prostatic
hyperplasia
24. G-protein-coupled receptors
Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands.
The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin.
Brain, Spinal cord and in digestive track
δ-opioid receptor Leu-enkephalin
Met-enkephalin
Deltorphins
Norbuprenorphin
μ-opioid, δ-opioid, and nociceptin receptor full agonist
Antagonists
Agonists
Buprenorphine
Trazodone
delta (δ) kappa (κ) mu (μ) Nociceptin receptor
•analgesia
•antidepressant effects
•convulsant effects
•physical dependence
•μ-opioid receptor-mediated
respiratory depression
25. G-protein-coupled receptors
There are two principal signal transduction pathways involving the G protein–coupled receptors:
•the cAMP signal pathway and
•the phosphatidylinositol signal pathway
•Class A (or 1) (Rhodopsin-like)
•Class B (or 2) (Secretin receptor family)
•Class C (or 3) (Metabotropic glutamate/pheromone)
•Class D (or 4) (Fungal mating pheromone receptors)
•Class E (or 5) (Cyclic AMP receptors)
•Class F (or 6) (Frizzled/Smoothened)
26. Glutamic acid, GABA, noradrenaline, dopamine, acetylcholine, serotonin, prostaglandins,
adenosine, endogenous opioids, angiotensin, bradykinin, and thrombin
Considering the structural variety of the chemical messengers involved, it is remarkable that the overall
structures of the G-protein-coupled receptors are so similar.
the amino acid sequences of the receptors vary quite significantly.
This implies that these receptors have evolved over millions of years from an ancient common ancestral protein
27. G-protein-coupled receptors activate signal proteins called G-proteins. Binding of a messenger results in the
opening of a binding site for the signal protein. The latter binds and fragments, with one of the subunits
departing to activate a membrane-bound enzyme
The G-protein-coupled receptors are membrane-bound proteins with seven transmembrane sections. The C -
terminal chain lies within the cell and the N -terminal chain is extracellular.
The location of the binding site differs between different G-protein-coupled receptors
The rhodopsin-like family of G-protein-coupled receptors includes many receptors that are targets for currently
important drugs.
Receptor types and subtypes recognize the same chemical messenger, but have structural differences,
making it possible to design drugs that are selective for one type (or subtype) of receptor over another.
Receptor subtypes can arise from divergent or convergent evolution.
33. Kinase-linked receptors are receptors which are directly linked to kinase enzymes. Messenger binding
results in the opening of the kinase-active site, allowing a catalytic reaction to take place.
Tyrosine kinase receptors have an extracellular binding site for a chemical messenger and an intracellular
enzymatic active site which catalyses the phosphorylation of tyrosine residues in protein substrates.
The insulin receptor is a preformed heterotetrameric structure which acts as a tyrosine kinase receptor.
The growth hormone receptor dimerizes on binding its ligand, then binds and activates tyrosine kinase
enzymes from the cytoplasm.
