This webpage aims to present the findings of the Rasmussen et al paper: Crystal structure of the β2 adrenergic receptor–Gs protein complex.

Introduction to the beta-2 adrenergic receptor-Gs protein complex

What is the beta-2 adrenergic receptor?

Adrenergic receptors, also known as adrenoreceptors are a type of G protein-coupled receptor (GPCR). This protein family is involved in sensing molecules outside of the cell and activating an internal signal transduction pathway, ultimately determining a certain cellular response to that molecule. GPCRs are responsible for the senses of sight, smell and taste, as well as being responsible for the majority of cellular responses to neurotransmitters and hormones (Chung et al, 2011). These proteins are anchored to the cell membrane by 7 transmembrane domains. 

What is Gs?

Gs is the stimulatory G protein that activates adenylyl cylase. G proteins are also involved in transmitting signals from the outside of the cell to the inside, serving to act as 'molecular switches' depending on whether they are bound to GTP or GDP (the hydrolyzed form of GTP). They consist of three subunits: α, β and γ, which dissociate upon binding of GTP into separate α and βγ units. The alpha subunit then goes on to regulate its effector protein adenylyl cyclase, and the βγ subunit regulates the Ca2+ channels (Rasmussen et al, 2011).

This webpage will explore how a complex was made between these two proteins, the structure of this complex (shown in fugure 1), as well as showing us the structures of the proteins in their active and inactive forms.

Figure 1: Overall structure of complex. T4 Lysozyme (red) aids crystallization, Receptor: β2AR (green) bound to agonist (magenta). G protein bound to receptor consisting of Gα (blue), Gβ (orange) and Gγ (grey). Gs binding nanobody: Nb35 (yellow) bound to G protein between α and β subunits also aids the crystallization process.

References
Chung, K., Rasmussen, S., Liu, T., et al (2011) Conformational changes in the G protein Gs induced by the β2 adrenergic receptor. Nature. [Online] 477 (7366) 611-615. Available from: doi:10.1038/nature10488 [Accessed 7th December 2013)

Rasmussen, S., DeVree, B., Zou, Y., et al (2011) Crystal structure of the β2 adrenergic receptor–Gs protein complex. Nature [Online] 477, 549-555. Available from: doi:10.1038/nature10361 [Accessed 7th December 2013] - Used throughout