Final answer:
The first active GPCR to show X-ray crystal structure with its bound G protein was the β2-adrenergic receptor complexed with the Gs protein. This marked a milestone in understanding GPCR function and cellular signaling, aiding rational drug design.
Step-by-step explanation:
The first active GPCR to have its X-ray crystal structure determined with its bound G protein was the β2-adrenergic receptor in complex with Gs protein. This breakthrough in structural biology was significant because GPCRs are a large family of receptors that play a crucial role in cell signaling.
They are involved in many physiological processes and are a major drug target. The difficulty in crystallizing membrane proteins such as GPCRs stems from their dynamic nature and the necessity of membrane mimicking environments for their stability.
Using X-ray crystallography, scientists were able to reveal the arrangement of the seven transmembrane domains unique to GPCRs and understand how ligands binding to these receptors can activate associated G-proteins. This in turn initiates a cascade of cellular events. The crystal structure of the GPCR in complex with the G protein provided insights into the mechanism of GPCR activation and G protein coupling, thereby opening up new avenues for rational drug design.
It is worth recognizing that X-ray crystallography has been a revolutionary technique in structural biology, contributing to milestones such as the discovery of the double-helix structure of DNA. Similarly, the determination of the GPCR-G protein complex structure represents a landmark in the understanding of cellular communication and pharmacology.