Listen to the classic song while reading the post!
If you were born in the 1960’s and if you happen to do The Twist with your partner your heart would of course be racing! Thanks to G protein-coupled inwardly-rectifying potassium channels (GIRKs) your heart can beat back to normal levels. Ironically, the protein does a “twist” to slow down the heart. Go Figure!
GIRK is basically a potassium ion-transporter and found in cardiac cells. It regulates the membrane voltage after the GPCR activated G-beta and G-gamma bind to the transporter.
In this groundbreaking work, three structures were used to understand the dynamics of the transporter.
- The normal GIRK transporter
- The GIRK bound with G-gamma, and
- A GIRK mutant (R201A) that is always in the open conformation.
The mechanism of transporting the K+ ion across the membrane starts after the G-beta and G-gamma bind to GIRK, and thus getting a twist of 4 degrees clockwise (looking from inside the cell). This is observed as a highly energetic, but stable conformation. In other words, a “meta-stable” form. It is just waiting for a “spark” (binding of Na+ ion), due to which it twists further to open the channel to a wider 9 degrees, thereby allowing the K+ to be transported across the membrane.
This twisting and untwisting continues till the resting potential (Nernst K+) is reached, thus slowing the firing frequency in pacemaker cardiac cells, resulting in slower heart rate.
The coordinates of the GIRK-G-gamma complex will be released soon. LINK
- Whorton, M., & MacKinnon, R. (2013). X-ray structure of the mammalian GIRK2–βγ G-protein complex Nature DOI: 10.1038/nature12241