receptors Flashcards
what are the 4 main receptor classes?
- ligand-gates ion channels (ionotropic receptors)
- G protein-coupled receptors (metabotropic)
- kinase linked receptors
- nuclear receptors
why are receptors important?
- specificity
- sensitivity
- co-operativity
- amplification
- time-frame
how long does each receptor take to respond?
- ligand-gated channels: milliseconds
- g protein coupled: seconds
- kinase-linked: hours
- nuclear: hours
why ligand gated channels and G protein coupled receptrs respond quicker?
ligand-gated:
Direct ligand binding opens channels, allowing ion flow (Ca²⁺, Cl⁻, K⁺, Na⁺).
No secondary messengers involved.
Ion flux directly changes the membrane potential or triggers immediate cellular responses.
Speed: Response in milliseconds.
g protein coupled:
Ligand binding activates GPCR, which exchanges GDP for GTP on G-proteins within seconds.
Activated G-proteins regulate downstream effectors (e.g., enzymes or ion channels).
Effector activation produces second messengers like cAMP or IP3, amplifying the signal.
Signal amplification ensures a strong and fast response.
Speed: Response in seconds to minutes.
why do kinase-linked receptors and nuclear receptors take longer to respond?
Kinase-Linked Receptors:
Ligand binding triggers receptor dimerization and autophosphorylation.
Activation of multiple signaling cascades (e.g., MAPK, PI3K) involving several intermediate proteins.
Involves phosphorylation and protein-protein interactions, which take time to propagate.
Speed: minutes to hours
Nuclear Receptors:
Ligand (e.g., steroid hormones) diffuses into the cell and binds to the nuclear receptor.
The receptor-ligand complex moves to the nucleus and binds to DNA.
Activates gene transcription, requiring time for mRNA and protein synthesis.
Speed: hours to days due to the need for transcription and translation.
describe the structure and function of nuclear receptors
N-terminal domain:
- highly variable in amino acid sequence and length
- conatins AF1 invlved in transcription activation
- recruits c-activators/repressors
- regulates gene expression in respond to ligand binding
c-domain/ dna-binding domain:
- contains 2 zinc finger motifs
- these allow binding to Hormone Receptor Elements (HREs)
- regulates transcription
ligand-binding domain:
- Hydrophobic pocket for ligand binding
- ligand binding activates receptors which induces a conformational change
- Contains short helical structyre called AF-2 to recruit co-activators and activate transcription.
- Recruits co-regulators
what are the main differences between type 1 and type 2 nuclear receptors?
Type 1:
- steroid hormones (oestrogen, cortisol), endocrine in nature
- before ligand binding found in cytoplasm
- when a ligand binds, the receptor dissociates from Heat Shock Proteins (HSPs) and forms homodimer
- receptor-ligand complex translocates to nucleus and binds to HREs in DNA to activate gene transcription
hours to days
Types 2:
- ligands are usually lipids
thyroids, retinoids, vitamin d
- found in the nucleus
– already bound to DNA as heterodimers with retinoid x receptor (RXR)
- induces conformational change, enabling gene transcription/repression
- co-repressors released/ co-activators recruited
- faster than type 1 (hours)
key feature sof ligan gated channels
Ligand-binding opens the channel, allowing ion flow.
Fast signaling (milliseconds).
Ion selectivity: Different channels allow specific ions to pass.
Excitatory or inhibitory depending on ion flow (e.g., Na⁺ for excitation, Cl⁻ for inhibition).
Essential in synaptic transmission for both neurons and muscle cells.
describe the structure of kinase linked receptors
extracellular domain:
- ligand binding region that interacts with specific molecules e.g growth factors
transmembrane domain:
- single pass through plasma membrane to anchor receptor
- intracellular domain:
- conatina kinase activty intrinsic or associated w other moelcules) thats activated when ligand binds
describe kinase linked receptor mechanism of action
- ligand binds to receptor
- this induces receptor dimerisation or oligomerization
- leading to autophosphorylation
- specifically tyrosine resides are phosphyrlated and these serve as docking sites for signal transducers such as proteins with SH2/PTB domains
- intracellular pathways activate dlike MAPK, PI3K,JAK/STAT
- leads to signal amplification
describe structure of EFGR
Extracellular Domain:
Binds to epidermal growth factor (EGF) or related ligands.
Binding causes conformational changes, enabling receptor dimerization.
Transmembrane Domain:
A single alpha-helix anchors the receptor in the membrane.
Intracellular Tyrosine Kinase Domain:
Contains intrinsic tyrosine kinase activity that becomes activated upon dimerization.
Responsible for phosphorylation of tyrosine residues in the receptor’s C-terminal tail.
ok describe egfr activation
egfr to ras pathway
describe structure g protein-coupled receptors
- contain 7 transmembrane domains
- extracellular domain binds to ligands
- intracellular domain interacts with G proteins
describe the mechanism of action of G protein-coupled receptors
