G Protein Coupled Receptors
G Proteins-Coupled Receptors
The largest family of cell surface receptors.
Have 7 transmembrane segments ⟶ called 7-pass receptors.
Zigzag arrangement in like a snake ⟶ called serpentine receptors.
On extracellular side: Bind with a ligand.
On intracellular side: Associate with G protein.
G Proteins
Bind with GTP/GDP ⟶ Called GTP binding proteins or G protein.
Have GTPase activity.
Switch between two states:
GDP bound state: Inactive
GTP bound state: Active
Broad types:
Heterotrimeric G proteins.
Monomeric G proteins.
Heterotrimeric G Proteins
Composed of 3 subunits
α
β
γ
α subunit has GTPase activity.
Entire complex is anchored to the membrane with α and γ subunits.
Types:
Gs
Gi
Gq
Go
Different types have different sets of α, β, and γ subunits.
Mediates response to a wide range of signaling molecules including hormones, neurotransmitters, odorants, tastants etc.
Monomeric or Small G Proteins
Composed of a single subunit.
The subunit is similar to α subunit that is seen in heterotrimeric G proteins ⟶ has GTPase activity.
Families:
Ras
Rho
Rab
Arf
Ran
Regulate gene expression, dell proliferation, differentiation and survival
Cyclic Journey of Heterotrimeric G Protein
During signaling, subunits of G protein go through a cyclic path.
As they go through the cycle, they affect different downstream second messengers.
Resting Condition
Trimer of α, β and γ subunit is associated with the receptor.
α subunit is bound to GDP
Activation and Signaling
Ligand binds with the receptor
↓
Conformational change
↓
Release of GDP and binding of GTP to α subunit
↓
Dissociation of the complex from receptor & separation of subunits
↓
Formation of free α subunit and βγ complex
↓
Interact with different downstream molecules e.g. α subunit interacts with adenylyl cyclase and βγ complex interacts with ion channels
↓
The signal is carried further downstream
↓
Response
Inactivation
GTPase activity of α subunit
↓
Hydrolyses GTP into GDP and phosphate
↓
Inactive α subunit
↓
Dissociates from the downstream messenger
↓
Re-associates with βγ complex
↓
Termination of the signal