Cell receptors Flashcards
What are cell receptors (5)
- Membrane-bound or intracellular
- Protein molecules that communicate signals
- Activated by molecules known as ligands
- Distribution and concentration vary in different tissues/organs.
- Therapeutic targets
How does receptor activation work (7)
- Lock and key hypothesis” – based on structural similarity
- Key = ligand
- Lock = receptor
- correct fit = receptor activation
- incorrect fit = no receptor activation
- Chemical interactions occur between receptor and ligand
- SPECIFICITY and SELECTIVITY of ligand-receptor interactions
What are the chemical interactions between ligand and receptor (4)
- Electrostatic interactions
- Hydrophobic interactions
- Stereospecific interactions
- Covalent bonds
What are the main types of receptors (5)
- G-protein coupled receptors
- Tyrosine kinase receptors
- Nuclear receptors
- Ligand-gated ion channels
- Voltage-gated ion channels
What are G-protein coupled receptors (GPCR) and an example (5)
- Trans-membrane and integral membrane proteins
- Receptor coupled with a G-protein
- Wide variety of different GPCRs binding a range of ligands
- Ligands bind to extracellular domains, and signal transduction is activated intracellularly.
- Example: beta2-adrenoceptors
What are G-proteins (3)
- guanine nucleotide-binding regulatory protein
- Signal transducer – from receptor to effector
- Heterotrimer (alpha, beta, gamma subunits)
What are G-protein regulated effectors (2)
- Enzymes (e.g. adenylyl cyclase, phospholipase C and cGMP phosphodiesterase)
- Some ion channels
What are examples of an inactive and active G-protein (3)
- Inactive G-protein = alpha-GDPbeta-gamma
- Active G-protein = alpha-GTPbeta-gamma
- The affinity of the alpha subunit changes with ligand-GPCR binding.
What are second messengers (4)
- Small molecules
- Formed in response to the activation of some receptors
- Example includes: Cyclic nucleotides (cAMP) (via Adenylyl cyclase)
- Receptor agonist = First messenger
What are tyrosine-kinase receptors and what is an example (5)
- Trans-membrane proteins (two monomer units dimerise)
- Contain enzyme activity within receptor proteins – tyrosine kinases
- Monomers within the dimer cross-phosphorylate
- signals intermediary signalling proteins that activate signalling pathways
- Example: Insulin receptor
How do tyrosine-kinase receptors work (3)
- Activated receptor can accept phosphate groups from ATP to form ADP
- Intermediate proteins can obtain a phosphate group from the activated tyrosine-kinase receptor which in turn activates the intermediate receptor
- This triggers a ‘phosphorylation cascade’ resulting in a cellular response (via regulation of gene expression)
What are nuclear receptors and an example (4)
- Intracellular receptors
- Agonists enter the cell – lipid soluble
- The ligand-receptor complex enters the nucleus and alters gene expression
- Example: steroid receptors
What are ion-channel receptors (7)
- Ligand-gated AND Voltage-gated receptors
- Receptor and effector (ion channel) are part of the same transmembrane protein
- Binding of agonist results in the opening on the ion channel → membrane depolarisation
- Fast responding – in excitable cells
- Selective for which ions they allow to cross the membrane (Na+, Ca2+, K+, Cl-)
- Rely on there being a concentration gradient of the particular ion across the membrane.
- At rest there is ~ -70mV charge across the cell membrane
How do ligand-gated receptors work and what is an example (3)
- The opening of the ion channel is dependant on the appropriate ligand binding
- Ligand binding can occur extracellularly (first messengers) or intracellularly (second messengers)
- Example: nicotinic Acetylcholine receptor (nAChR)
How do voltage-gated receptors work and what is an example (4)
- The opening of the ion channel is dependant on the change in the cell membrane potential
- Size of depolarisation affects which voltage-gated channels open
- Go through a refractory phase **post re-closing
- Example: L-type Ca2+ channel