Chemical Signalling 2 Flashcards
What kind of signalling molecules associate with plasma membrane receptors?
Hydrophilic
What types of receptors are found in the plasma membrane?
Ligand gated ion channels
GPCR
Intrinsic enzyme receptors
What is the intracellular receptor present on the endoplasmic reticulum?
Ryanodine receptor (detects redox state of cell)
What is another name for an intrinsic enzyme receptor?
Pleiotropic receptor
Catalytic receptor
Which terminals are the ligand and enzyme domains?
Ligand = N
Enzyme = C
What is the structure of an insulin receptor?
Dimer connected by disulphide bridges
What is the structure of a nerve growth factor receptor?
Two single monomers that dimerise after bonding with agonist
Describe the process of RTK receptors
- Ligand binds receptor
- Conformational change of receptor results in autophosphorylation at tyrosine residues
- Adaptor protein binds to phosphorylated tyrosine and RAS-activating protein binds to adaptor (scaffold)
- Recruitment of RAS (G-protein)
- GDP is exchanged for GTP on RAS protein (activation)
- Triple phosphorylation of MAP kinase
- MAP kinase phosphorylation results in protein phosphorylation/changes in gene transcription
Which key enzymes’ phosphorylation patterns are altered in insulin signalling?
MAP kinase
Protein phosphatase 1
What does ZAC stand for?
Zinc-activated channel
What are the three types of ionotropic receptors?
Trimeric
Tetrameric
Pentameric
What is the structure of a trimeric ionotropic receptor? (4)
N and C terminals inside cell
Ligand-binding site outside cell
Second TM protein involved with pore
Three 4TM monomers
What is the structure of a tetrameric ionotropic receptor? (4)
N terminal outside, C terminal inside
Four 3TM monomers
Loop between first and second TM proteins in a monomer involved in pore
Ligand-binding site outside cell
What is the structure of a pentameric ionotropic receptor? (4)
Ligand-binding site outside cell
Both C and N terminals outside cell
Five 4TM monomers
Second TM protein involved in pore
Give an example of a pentameric ionotropic receptor
Nicotinic R-like/cholinergic
Give an example of a trimeric ionotropic receptor
ATP receptor channel
P2X receptors
Give an example of a tetrameric ionotropic receptor
Ionotropic glutamate receptor
NMDA receptor
AMPA receptor
Kainate receptor
Why can’t ions pass through closed pores/ionotropic receptors?
Hydrophobic amino acid side chains face into pore
Ions have hydration shells
Hydrophilic ions can not pass hydrophobic pore
Give an example of a nuclear receptor agonist
Steroid hormones
Thyroid hormones
Vitamin D
Retinoic acid
Oestrogen
Glucocorticoid
Describe the process of nuclear receptor signalling
- Ligand passes through plasma membrane and binds with nuclear receptor in cytosol
- Dimerisation of ligand-bound nuclear receptors
- Translocation (dimer moves into nucleus)
- Receptor binds with DNA using zinc fingers
- Altered transcription
What is the structure of a nuclear receptor?
C terminal
Ligand-binding site
Zinc fingers
Coactivator region
N terminal
What is the role of glucocorticoids?
Anti-inflammatory
Inhibit transcription of cytokines (specifically interleukins)
Increase synthesis and release of annexin-1 (anti-inflammatory)
How long does it take for an ionotropic receptor’s effect to occur?
Milliseconds
How long does it take for a metabotropic GPCR’s effect to occur?
Seconds
How long does it take for a catalytic kinase-linked receptor’s effect to occur?
Hours
How long does it take for a nuclear receptor’s effect to occur?
Hours to days
Give two examples of RTKs
Insulin receptors
Nerve growth factor receptors (TrkA)
What kind of protein is RAS?
Monomeric G-protein
