Question

Describe the structure and function of the \(\alpha, \beta,\) and \(\gamma\) subunits of a heterotrimeric G protein.

Short answer

Answer: In a heterotrimeric G protein, the α subunit primarily regulates the activity of effector proteins by binding to GDP (inactive state) or GTP (active state), resulting in an activation or inhibition of the effector depending on the type of α subunit. The βγ dimer is essential for stabilizing the inactive state of the G protein, facilitating the exchange of GDP for GTP in the α subunit, and contributes to the specificity of the signaling by selecting and activating specific GPCRs. Additionally, the dissociated βγ dimer can directly regulate the activity of certain effector proteins, such as ion channels and enzymes.

Step-by-step solution

Introduce heterotrimeric G proteins

Heterotrimeric G proteins are specialized proteins involved in signal transduction pathways, which are cellular processes through which external signals (like hormones or neurotransmitters) are transmitted inside a cell, leading to a specific response. Heterotrimeric G proteins consist of three different subunits, the alpha (α), beta (β), and gamma (γ) subunits.

Describe the structure of the α subunit

The α subunit is a larger protein than both β and γ subunits. The structure consists of a single polypeptide chain folded into a compact globular shape. It binds GDP (guanosine diphosphate) in its inactive state and GTP (guanosine triphosphate) in its active state. The subunit also has a crucial lipid modification called a myristoyl group or a palmitoyl group at the N-terminus, which helps anchor the protein to the cell membrane.

Describe the structure of the β and γ subunits

The β and γ subunits are smaller proteins and closely associated with each other in a stable complex called the βγ dimer. This dimer has an elongated structure composed of two parallel strands of β sheets. Like the α subunit, the γ subunit also has a lipid modification at its C-terminus, a prenyl group, which helps anchor the dimer to the cell membrane.

Explain the function of the α subunit

The primary function of the α subunit is to regulate the activity of its target proteins called effectors, which can be enzymes or ion channels. In its inactive state, the α subunit binds GDP and associates with the βγ dimer. Upon binding to an activated G protein-coupled receptor (GPCR), the GDP is exchanged for GTP and undergoes a conformational change in the α subunit. This change causes dissociation from the βγ dimer and interaction with the effector proteins, activating or inhibiting their function depending on the type of α subunit.

Explain the function of the βγ dimer

The βγ dimer is essential for stabilizing the inactive state of the G protein. It also has a regulatory role in the activation of the G protein by facilitating the exchange of GDP for GTP in the α subunit. Both the β and γ subunits play a role in selecting and activating specific GPCRs, contributing to the specificity of the signaling. In some cases, the dissociated βγ dimer can also directly regulate the activity of certain effector proteins such as ion channels and certain types of enzymes.

Recap the functions of the subunits

In summary, the α, β, and γ subunits of a heterotrimeric G protein function together to transmit signals inside the cell. The α subunit regulates effector proteins' activity with its GTP/GDP binding state, while the βγ dimer stabilizes the inactive state and facilitates activation. Both α and βγ subunits can regulate specific target proteins, contributing to the specificity and diversity of GPCR signaling pathways.