There are more than 800 GPCRs in humans that signal through around 20 diverse G proteins. GPCRs are responsible for sensing a wide scope of outside signals-, for example, hormones, light, and sense of smell and taste – and actuating corresponding responses inside the cell.
In the vertebrate vision, the GPCR rhodopsin is equipped for identifying the sign from only one photon and through the initiation of the G protein transducin and downstream effectors, enhance it multiple times.
Now, scientists have solved the three-dimensional structure of a protein complex involved in the vertebrate vision at atomic resolution.
According to scientists, the study has broad implications for our understanding of biological signaling processes and the design of over a third of the drugs on the market today.
The discoveries enlighten how signals from photons (particles of light) get amplified in the eye. Also, the study gives detail insights into how the largest family of cell membrane proteins – G-protein-coupled receptors (GPCRs) – work in humans.
Yang Gao, co-first author of the paper said, “They’re involved in almost all the biological processes in a human body — how we perceive light, taste, smell, or how the heart rate is regulated or muscles contract — and they are targets for over 30% of the drugs that are used today.”
For the study, scientists used cryo-electron microscopy technique to get atomic-resolution structures of the rhodopsin-transducin complex. The structures did not just give the molecular basis of vertebrate vision, yet additionally, uncover a previously unknown mechanism of how GPCRs, in general, activate G proteins.
Co-first author Sekar Ramachandran, a senior research associate in Cerione’s lab, said, “What we’ve learned from these structures at an atomic level may be broadly applicable to other GPCR signaling systems.”
“By learning more about how different receptors, specifically couples with different G proteins, we hope to gain insights into designing drugs that specifically regulate GPCR signaling. A lot of drug side effects occur when therapies are not specific enough and target both harmful and beneficial pathways.”
The study is published in the journal Molecular Cell. Hongli Hu, a postdoctoral researcher in Stanford’s Department of Structural Biology, is a co-first author; Georgios Skiniotis, professor of molecular and cellular physiology and structural biology at Stanford, is a co-senior author.