3 - G protein coupled receptors

What is the structure of ‘most’ G proteins?

Trimeric membrane associated protein containing α, β and γ subunits

What is the interactions of β and γ subunits in G proteins?

Tightly bound to each other and operate as a single entity 

What can the α subunit do, in G protein?

Can dissociate and operate on its own  

What is added to G protein subunits after translation?

Lipid tails

When are lipid tails added onto G protein subunits?

After translation

What do lipid tails on G proteins do?

Anchor G protein subunits to the membrane

What are the 2 alt names for the GPCR superfamily?

Serpentine receptors / 7 transmembrane domain receptors

M1, M3, M5 only bind to______?

Gq

M2, M4 only bind to ______?

Gi

What is the most prominent structural feature of GPCRs?

Their membrane topology (how they are arranged across the membrane)

G protein binding site on intracellular face of GPCR is NOT _________?

Universal

Why is specificity important?

Because cells contain multiple types of G protein / allow cell to respond to different extracellular signalling molecules

What are orphan receptors?

Receptors with no identified natural ligand?????

What happens when a natural ligand to an orphan receptor is identified?

Receptor is deemed to be de-orphanismed / adopted

Which intracellular messenger is involved in the GPCR signal pathway.

cAMP

Which 2 G proteins is cAMP linked to?

Gs / Gi

What does the conc.of cAMP inside cell depend on?

Adenylyl cyclase activity & PDE

What is PDE abbreviated for?

Phosphodiesterase

What does PDE do to cAMP?

Break down to AMP

What can inhibit PDE?

Caffeine

Where is PKA found?

Cytoplasm

PKA is found in the cytoplasm as an_________________________?

Inactive tetramer, consisting 2 catalytic subunits + 2 regulatory subunit

What do PKA do to target proteins?

Phosphorylate serine & threonine residues in target protein, altering their activity.

What needs to happen to PKA for their catalytic subunits to be released / activated?

When regulatory subunits each bind 2 molecules of ATP

What type of tissues for intracellular targets of PKA found in?

Skeletal, cardiac muscle / hepatocytes / adipocytes / kidney cell types

Which ion channels can cAMP bind to?

HCN channels in the heart and modulate their activity / v.important in pacemaker currents in SA node

Which membrane enzyme is involved in the GPCR signalling pathway that is linked to Gq?

Phospholipase C

What does phospholipase C do?

Cleaves membrane lipids, result in direct formation of 2 different 2nd messenger

How does signalling via Gq differ from Gs / Gi?

As it coupled to INTRAcellular pathways via two 2nd messengers

What are the two 2nd messengers formed in signalling via Gq?

diacylglycerol & inositol triphosphate / DAG & IP3

What does IP3 do?

Increase intracellular [Ca2+] / Ca2+ can also act as a 2nd messenger

What is the cytoplasmic concentration of Ca2+?

Kept v.low

How do cells achieve control over the concentration of Ca2+?

Actively pumping it into stores: ER / mitochondria

HOW do IP3 increase Ca2+ conc.?

By binding to, and open a Ca2+ channel that is heavily expressed in the ER

How does Ca2+ act as a 2nd messenger?

Ca2+ released from IP3 receptors can then activate another Ca2+ channel (ryanodine receptor)

What are the 2 receptors, that are also Ca2+ channels?

IP3 receptor / ryanodine receptor

What ion channel are ryanodine receptors?

Ca2+ channel

What ion channel are IP3 receptors?

Ca2+ channel

What does CICR stand for?

Calcium induced calcium release

What are ryanodine receptors?

Calcium sensitive calcium channel

What is the name of the process that activates ryanodine receptors? (abbreviated)

CICR