No 3D structure for peculiar protein
25 Jun 2012 by Evoluted New Media
An unusual protein which lacks any definable structure – defying the long-held notion that a protein’s precise 3-dimensional structure determines its function – helps regulate a key cell communication pathway say researchers in America.
Researchers from Washington University School of Medicine have unveiled some of the inner workings of certain potassium channels involved in regulating electrical signals in nerve cells, relaxing muscle cells and tuning hair cells in the inner ear.
The protein plays a key role in temporarily blocking the movement of ions through large potassium channels called BK channels after a cell fires off an electrical signal. Blocking the movement of ions through the channel gives the cell time to recharge so that they can continue firing.
Researchers – led by CJ Lingle, a professor of anaesthesiology and neurobiology – found that the protein responsible for inactivating the BK channel was intrinsically disordered, defying the long-held belief that a protein’s function was determined by its precise 3-dimensional structure.
By monitoring the electrical activity of BK channels as they opened and closed, the researchers found – despite its disordered structure – the protein nestles into a receptor inside the BK channel in a highly specific way.
“My guess is that the part of the protein that binds to the potassium channel receptor may have to move through some very narrow spaces,” said Lingle. “It may be that by having a less-defined structure, the protein can navigate more easily through tight spaces and to get to the binding site.”
“It’s a two-step process, which distinguishes it from most other inactivation mechanisms that have been described.”
Researchers are now hoping to learn more about the physiological effects of BK channel behaviour in mouse cells. Since BK channels are known to be involved in epilepsy, asthma and cardiovascular disease, a better understanding of how they operate may help scientists discover new ways to treat these conditions and determine why disordered protein domains that regulate these channels don’t have a well-defined structure.
Stereospecific binding of a disordered peptide segment mediates BK channel inactivation
