Intracellular Signalling (Receptor and Effector Mechanisms) Flashcards
What is signal transduction?
A basic process in molecular cell biology involving the conversion of a signal from outside the cell to a functional change within the cell.
Where are receptors usually located?
The cell-surface, however some can be intracellular
What are G protein-coupled receptors also known as?
Seven-transmembrane domain (7TM) receptors
What is a ligand?
Ligand interact with receptors - ligand binding activates the receptor, which in turn directly or indirectly brings about a change in cellular activity
What is an agonist?
Agonists bind to the receptor and activate it, leading to intracellular signal transduction events
What is an antagonist?
They bind to the receptor but do not activate it, they block the effects of agonists at the receptor
What is the difference between affinity and efficacy?
Affinity = how well it binds to the receptor Efficacy = how well it causes the response
What is the common basic structure of all GPCRs?
- Single polypeptide chain (300-1200 amino acids)
- 7 transmembrane spanning regions
- Extracellular N-terminal
- Intracellular C-terminal
Which two regions of GPCRs can be responsible for ligand binding?
For some receptors the ligand binding site is formed by (2-3 of) the transmembrane domains
In other cases the N terminal region form the ligand binding site
What happens when the ligand binds?
It changes the conformation of the transmembrane domains which turns the receptor ‘on’. Acivated GPCR facilitates GTP-GDP exchange on the alpha subunit of the G protein.
What is a G protein?
Guanine-nucleotide binding protein - interacts with GPCR and made up of three subunits (heterotrimeric)
So G proteins able to bind with GTP, GDP etc
What happens when the G protein interacts with the ‘on’ GPCR?
The alpha - beta/gamma complex immediately dissociates as they lose affinity for each other and then each interact with effector proteins
What governs Receptor-G protein selection?
Activated GPCRs preferentially interact with specific types of G protein. The alpha subunit is a primary determinant.
In this way, an extracellular signal working via a specific GPCR will activative a single G protein and effectors in the cell to bring about a specific cellular response
Which 2 subunits of the G protein are attached to the cell membane via lipid anchors?
Alpha subunit and Gamma subunit
When the G protein is inactive does it bind GDP or GTP?
GDP (binds to alpha subunit)
What initially happens when the ligand binds to the GPCR?
Conformational change
Briefly describe the steps that follow a ligand binding to a GCPR
1) Ligand binds
2) GPCR undergoes conformational change
3) Alpha subunit exchanges GDP for GTP
4) Alpha subunit dissociates from beta/gamma
5) Subunits go on to regulate target proteins
6) GTP hydrolysed to GDP and subunits rejoin
What are some examples of β2 adrenoceptor agonists?
Salbutamol, Salmeterol
Anti-asthma
What are some examples of μ-opioid receptor agonists?
Morphine, Fentanyl
Analgesia/anaesthesia
What are some examples of β adrenoceptor antagonists?
Propranolol, atenolol
Cardiovascular (hypertension)
What are some examples of D2 dopamine receptor antagonists?
HALOPERIDOL, SULPIRIDE
neuroleptics (anti-schizophrenic)
Is the N terminal of a GPCR extracellular or intracellular?
Extracellular
Is the C terminal of a GPCR extracellular or intracellular?
Intracellular
What does the alpha s subunit of a Gs protein do?
Stimulates adenylyl cyclase
