M&R - Receptors in Cell Signalling Flashcards
What is a receptor?
A molecule that recognises a specific ligand or family of ligands
The ligand binding brings about regulation of a cellular process.
What is a ligand?
A small molecule that binds to a receptor site that’s may produce activation of a receptor or may bind to the receptor site without causing activation
What is an acceptor?
Molecules that their basic function can be carried out without the interaction of a ligand (NOT receptors)
Where must the receptor be if receiving a hydrophilic signal?
On the cell surface
Where must the receptor be for a hydrophobic signal?
Intracellular receptor
How are receptors classified?
According to the agonist and then sub classified on the basis of affinity
What are 5 similarities between receptor binding sites and enzyme substrate binding sites
- Binding at both sites is specific
- Specificity is governed by the shape of the site
- Specificity of binding = specificity of regulation
- Binding is most often reversible
- Ligand binding and allosteric sites on enzymes induces a conformational change
What are some differences between receptor binding and enzyme sites?
- Affinity of ligand binding at receptor sites is higher than the binding at enzyme sites
- The ligand bound to a receptor site is not modified chemically wheras the substrate bound in an enzyme AS is modified
What are the 4 common mechanisms for receptor action?
- Membrane bound receptors with integral ion channels
- Membrane bound receptors with integral enzyme activity
- Membrane bound receptors which couple effectors through transducing proteins
- Intracellular receptors for hydrophobic ligands
Briefly describe how membrane bound ion channels with integral ion channels work?
Ligand binding results in conformational change and opening of ion channel which permits ion flow down EC gradient.
E.g nicotinic acetyl choline receptors
Briefly describe how membrane receptors with integral enzyme activity work
This is when the agonist binding causes a conformational change which activates an intrinsic enzyme activity
E.g tyrosine kinase linked receptors
Explain how seven transmembrane domain receptors work
Receptor binding results in a conformational change which activates transducing molecule (G protein ) These couple to effector molecules ie enzyme to bring about change
E.g ATP –> cAMP
Briefly describe how intracellular receptors work
Hydrophobic ligands penetrate PM and bind to cytoplasmic or nuclear receptors. Chaperone protein dissociates and receptors translocates to the nucleus where it binds to DNA control regions - regulating gene transmission
What is amplification?
By the stimulation of an enzyme this causes modification of thousands of substrate molecules - enzyme cascade!
What is phagocytosis?
Permits the clearance of damaged cellular material
Particle binds to PM receptors
Cell extends pseudopods which internalise the particle
Phagosome fuse with lysosomes to form phagolysosomes in which the material is degraded
What is pinocytosis?
Invagination of the PM to form a lipid vesicle
Permits the uptake of impermeable Extracellular solutes
What is receptor mediated endocytosis?
Subtype of pinocytosis
Specific binding or molecules to cell surface receptors permits selective uptake into the cell
Where are receptors located on the plasma membrane?
Over the coated pits
Describe the process of cholesterol uptake
LDLs - apoprotein B on the surface - recognised by LDL receptors (clustered over coated pit) these invaginate and pinch off from PM to form coated vesicles. They are quickly uncoated and fuse with ENDOSOMES (pH of these are low due to ATP - H+ pump) at this low pH ligand and receptor uncouple
What happens to the LDL receptor after uncoupling in the endosome?
It buds off as a vesicle to be recycled
What happens to the free LDL after the endosome?
Fuses with lysosomes and the cholesterol esters are hydrolysed into Cholesterol and fatty acids
What is the structure of the coated pit?
Triskellion (clathrin and 2 light chains)
Forms a basket like structure of hexagons and pentagons
Assembly is spontaneous
What might some mutations that affect LDL uptake be?
Receptor deficiency
Non functional receptor
LDL receptors located away from the coated pit so no internalisation of the LDLS
How is iron uptaken into the cell?
2Fe3+ ions bind to apotransferrin forming transferrin
This binds to receptors and is internalised
On reaching the endosome the Fe2+ ions are released from transferrin but apotransferrin remains associated with the receptor until it is sorted and recycled back to PM and is dissociated at surface
