Receptors Flashcards
What kind of molecules target receptors?
Neurotransmitters
Hormones
Mediators eg peptide growth factors and chemokines
Therapeutic agents ie agonists, antagonists, allosteric modulators
Why do cells respond differently to the same ECF?
Different types of cells have different receptors in their membranes which have different ligands
What are the four main classes of receptors?
Type 1 - ligand-gated ion channels (LGICs)
Type 2 - G-protein-coupled receptors (GPCRs)
Type 3 - kinase linked
Type 4 - nuclear
What are ionotropic receptors?
Also known as transmitter-gated ion channels
Ligand-gated ion channels
What are metabotropic receptors?
G-protein-coupled receptors
Where are receptors found?
Plasma membrane
Intracellular membranes
Cytoplasm
Nucleus
Where are ligand-gated ion channels found?
What targets them?
Mostly plasma membrane, some in intracellular membranes (ER)
Hydrophilic signalling molecules (fast neurotransmitters)
Where are G-protein-coupled receptors found?
What targets them?
Plasma membrane
Hydrophilic signalling molecules (slow neurotransmitters and hormones)
Where are Kinase linked receptors found?
What targets them?
Plasma membrane
Hydrophilic protein mediators eg insulin and growth factors
Where are nuclear receptors found?
What targets them?
In cytoplasm (move to nucleus following activation) Hydrophobic signalling molecules (can cross plasma membrane unaided) eg steroid and thyroid hormones
What kind of protein makes up ion channels?
Transmembrane glycoprotein
Do ion channels require energy to allow ions to move to other side of membrane?
No, facilitated diffusion is passive
Are ion channels fast or slow?
Very fast, involved in rapid electrical signalling
What can (open) change the formation of a gated ion channel?
Chemical ligands
Voltage (membrane potential)
Physical stimuli (thermal and mechanical energy)
What are the three main types of Ligand-gated ion channels?
Pentamer
Tetramer
Trimer
Classified by number of subunits
Describe the structure of a ligand-gated ion channel?
Also known as ionotropic receptor
Separate glycoprotein subunits joining to form central channel through which ions can diffuse
What happens when a G-protein-coupled receptor is activated?
Signal reaches G-protein-coupled receptor
Receptor activated
Receptor activates G-protein
G-protein activates effector
Effector synthesise second messenger which targets something within the cell
How does the speed of GPCRs compare to LGICs?
GPCRs much slower
Stucture of GPCRs
What kind of protein is a GPCR?
How many polypeptides?
How many times does it span the membrane?
Do GPCRs ever work together?
Integral membrane protein
One polypeptide with NH2 terminus outside and COOH terminus inside
Spans membrane 7 times (3 loops inside, 2 loops outwith)
Two may function together as a dimer
Structure of G-protein
What kind of protein is it?
How many polypeptide subunits?
What kind of binding site?
Do multiple types exist?
Peripheral membrane protein
3 subunits
guanine nucleotide binding site in alpha subunit which can hold GTP or GDP
yes, depending on type of alpha subunit
How is a G-protein activated?
By an agonist binding to the GPCR
What occupies guanine nucleotide binding site when G-protein not activated?
GDP
What are the Ras and Ah subdomains in a G-protein?
Make up alpha subunit
Ras is GTPase
AH keeps nucleotide in place
How is a G-protein attached to plasma membrane?
Covalently bonded lipid molecules attached to membrane and alpha and gamma subunits
What is the beta subunit in a G-protein attached to?
Gamma subunit
Together they make a heterodimer
What happens when a GPCR is activated?
GCPR undergoes conformational change
This change is transmitted to G-protein alpha subunit
Alpha subunit releases GDP allowing GTP to bind
Alpha subunit of G-protein separates from GCPR and from other subunits (subunit dissociation)
Now both alpha subunit and beta-gamma heterodimer can act as free signals to other structures within cell
How is the signalling G-protein stopped?
GTPase changes GTP back into GDP so original form is regained
What happens if a beta-adrenoreceptor is activated by adenaline?
G(s) protein activated
Stimulates adenylyl cyclase to turn ATP into cAMP
cAMP activates kinase A
Kinase A phosphorylates Ser/Thr residures in target proteins
Causes cellular effect
What happens if a muscarinic acetylcholine receptor is activated by acetylcholine?
G(i) protein activated
Inhibits production of cAMP by adenylyl cyclase
What happens if an alpha 1 adrenoreceptor is activated by adrenaline?
G(q) protein activated
Stimulates phospholipase C (PLC) to turn PIP2 into IP3 and DAG
IP3 opens calcium ion channel in ER membrane
Ca2+ released causing cellular effects
DAG stimulates Protein Kinase C (PKC) to phosphorylate Ser/Thr residues in target proteins also causing cellular effects
What happens when Insulin binds to it’s kinase-linked receptor?
Causes autophosphorylation of intracellular tyrosine residues
Multiple adapter proteins recruited (IRS1 especially), these are also tyrosine phosphorylated
These proteins cause cellular effects
What are nuclear receptors?
Ligand-gated transcription factors
How do steroid hormones enter a cell?
By diffusion - they are hydrophobic and lipophilic
What do steroid hormones do in a cell?
Combine with intracellular receptor in cytoplasm causing inhibitory HSP protein to dissociate from receptor
Receptor-steroid complex moves into nucleus and forms a dimer with another complex
Dimer bonds to hormone response elements in DNA
Transcription of particular gene is either switched on (transactivated) or off (transrepressed)
