L4 - receptors Flashcards
list the (3) locations receptors can be located, and give examples for each
plasma membrane
-LGIC, GPCR, intrinsic enzymes
Intracellular receptors (on organnelle membranes, eg mitochondria or vesicles)
- Ryanodine receptors
- VMAT
- IP3
Nuclear receptors (which interact with DNA) - Steroid receptors
list the 4 functional types of receptors
LGIC
GPCR
intrinsic enzymes
Nuclear receptors
briefly desrcibe the basic fucntion of Ryanodine and IP3 receptors
LGIC that allow Ca2+ entry
give examples of nuclear receptors (DNA binding receptors)
oestrogen receptor
retinoic acid receptor
steroid receptors
describe structure of Nuclear receptors
LBS on the C terminal
dimerisation domain on the N terminus
between the dimerisation domain and the LBS there are zinc fingers
what is the importance of the dimerisation domain on nuclear receptors
receptors exist as monomers but dimerise with another ligand-bound receptor to become activated before entering the nucleus
describe the mechanism of nuclear receptor activation
- ligand binding to receptor activates it, but it must dimerise with another activated receptor before it can enter the nucleus
- after dimerisation the receptor can cross into nucleus and can alter expression of genes
- alters mRNA expression and so alters protein synthesis
where are intracellular membrane receptors found in neurones?
ER memrbane
describe ryanodine receptor
ligand gated calcium channel -> activated by Ca2+ (and some other ligands)
causes Ca2+ release from ER or SR (Ca2+ activated calcium release)
describe IP3 receptor
ligand gated Ca2+ channel - activated by 2nd messenger inositol 1,4,5 triphosphate (IP3)
causes Ca2+ release form ER or SR
where are IP3 and ryanodine receptors located?
membranes of SR or ER
list the types of plasma membrane receptors
LGIC
GPCR
intrinsic enzyme receptors
what are the 3 main types of LGIC families
Nicotinic receptor like
ATP receptors (P2X)
Ionotropic glutamate receptors
gove examples of Nicotinic R like ion channels
NAChR 5-HT3 GABA(A) Glycine ZAC (zinc activated)
how many types of P2x receptor are there
7
what is the difference between ATP P2x and P2Y receptors?
P2X -> the LGIC ATP receptors
P2Y -> the GPCR ATP receptors
what are the types of LGIC glutamate receptors
NMDA
AMPA
Kainate
descirbe structure of N R like receptors subunits TMD N&C terminal LBS pore?
5 subunits 4 TMDs extracellular N and C terminal N terminal LBS TMD2 is pore
descirbe structure of ATP receptors subunits TMD N&C terminal LBS pore?
3 subunits 2 TMDs intracellular N & C temrinal LBS on extracellular loop between the 2 TMDs pore in TMD2
descirbe structure of ionotropic glutamate receptors subunits TMD N&C terminal LBS pore?
4 subunits 3 TMDs extracellular N terminal intracellular C terminal LBS on large loop of N terminal inverted P loop between TMDs 1&2 which form the pore
what are the LGICs permeable to?
inhibitory ones (GABA & Glycine) -> Cl-
excitatory ones (most others) -> Na / Ca2+ in and sometimes K+ out
what aspect of the pore determines what ions can pass through?
the AA sequence and presence of ions (charge)
list the main 3 GPCR subfamilies (and give examples for each)
- Rhodopsin like (mACH, opioid, P2Y, all serotonin except 5-HT3)
- metabotropic Glutamate receptor like ( GABA(B), mGluRs)
- secretin receptor like (VIP, parathyroid hormone)
describe structure of Rhodopsin like GPCRs
- 7 TMDs
- extracellular N
- intracellular C
- G protein coupling region loop between TMD 5&6
- LBS small molecules (in TMDs)
- LBS larger molecules on extracellular N terminal
what structure are all TMDs
a helices
describe structure of metabotrophic glutamate like receptor
7 TMDs extracellular large looping N terminal intracellular C terminal G protein coupling region loop on TMD 2&3 LBS on large N terminal loop
found as dimers
the LBS will be found on one monomer and the G protein coupling region on the other
briefly describe GPCR function mechanism
- ligand will bind, activating receptor causing it to interact with G protein
- GDP converted to GTP causing G protein to dissociate (a and By)
- a subunit will diffuse and interact with enzymes in cytosol etc
By subunit can diffuse along membrane and act on ion channels
why does the By subunit of a g protein remain near membrane?
lipidation of AAs in By subunit cause it to stay close to membrane
list the two main types of intrinsic enzyme receptor families (and give examples)
receptor tyrosine kinases (insulin receptor)
receptor guanylyl cyclase (atrial natruiretic peptide)
what are intrinsic enzyme receptors
receptors that when activated act like enzymes
describe mechanism of intrinsic enzyme receptor activation
- ligand binding
- two ligand-bound receptors dimerise
- autophosphorylation - receptors phosphorylate eachother causing conformational change exposing the catalytic site of the receptors
- other substrates can then bind and be phosphorylates
describe process of receptor synthesis
- DNA -> RNA in nucleus
- RNA -> mRNA in rough ER
- mRNA -> protein in smooth ER (where N glycosylation occurs)
- protein O glycosylation occurs in Golgi
- protein sorted by sort system `
describe process of receptor sorting and trafficking
- all proteins have ‘sort sequence’ which allows their sorting by a sort system
- receptors are co transported with vesicles going to the same location, to where they need to be
(along with their G protein if they are a GPCR) - if the receptor is no longer needed or is damaged, it will travel back to where it originated from
(this wont be coupled to the G protein if its a GPCR)
how do rhodopsin like GPCRs and mGluRs differ?
rhodopsin has short N terminal mGluR has long N terminal
mGluR receptors often have to dimerise to become functional
their ligand binding is different
