1. Defintion
G-proteins (Guanine nucleotide-binding proteins) are molecular switches that transmit signals from receptors on the cell surface to internal signaling pathways. G-proteins are activated when they bind GTP (guanosine triphosphate) and inactivated when they hydrolyze GTP to GDP (guanosine diphosphate).
2. Biochemistry
When GTP is hydrolyzed, its γ-phosphate group is cleaved off, resulting in GDP and inorganic phosphate.
3. Classification
A distinction is made between membrane-bound heterotrimeric G-proteins and cytosolic so-called small G-proteins:
3.1. Heterotrimeric G-Proteins
Heterotrimeric G proteins are composed of three subunits (α, β and γ), with the α subunit having a GDP/GTP binding domain.
In the inactive form, the α subunit has GDP bound and is associated with βγ subunits. When it comes to ligand binding to the G protein-coupled receptor, the receptor changes its conformation. The result: the α subunit exchanges GDP for GTP (under the influence of GEF (guanine-nucleotide exchange factor)).
Now the α subunit dissociates from the βγ subunits, which will form another functional unit. In most cases, the α subunit will start different signal cascades (e.g. cAMP-cascade, inositol-phospholipid pathway). The βγ subunit will regulate effector proteins, as a functional unit.
3.1.1. Subfamilies:
- Gs: activation of the adenylate cyclase
- Golf: activation of the adenylate cyclase (especially in olfactory receptors of the olfactory epithelium)
- Gi: inhibition of the adenylate cyclase
- Gq: Phospholipase C-coupled G proteins -> activation of Phospholipase Cβ
3.2. Small G-Proteins
Small G-proteins (also known as small GTPases) are monomeric GTP-binding proteins with a molecular mass of 20 to 40 kDa. Currently, more than 100 different small G-proteins are known.
They are divided into 5 families: Ras, Rho, Rab, Sar1/Arf and Ran.
The small G-proteins are involved in numerous cell functions as well as cell growth, cell differentiation and lipid vesicle transport.