The transport system inside living cells is a well-oiled machine. It's got tiny protein motors hauling around chromosomes, neurotransmitters and other vital cargo.
While these molecular motors are responsible for a variety of critical transport jobs, they are not always on the go.
They can put themselves into "energy save mode" to conserve cellular fuel.
A new study by Carnegie Mellon University biochemists, published in the Aug. 12 issue of Science, describes how the motors fold in on themselves, or save energy, when their transport services aren't required.
According to the researchers, the solution to this molecular puzzle provides new insight into how molecular motor proteins are regulated.
It may open new avenues for the treatment of various neurodegenerative diseases, such as Alzheimer's and Huntington's.
"Molecular motor proteins play a major role in all eukaryotic cells, but they are particularly critical to nerve cells," said David Hackney, professor of biological sciences in the Mellon College of Science, and one of the paper's authors.
"Nerve cells have this special problem where proteins, such as receptors for neurotransmitters, get synthesized in the cell body and have to be shipped all the way down the axon. Problems in this transport system may play a role in a number of neurological conditions."
Hackney focuses his research on kinesin-1, the principle motor protein that moves cargo from the nerve cell body down the axon.
A typical kinesin molecule has two tails on one end that attach to the cargo and two globular heads on the other end that crank along fibers inside the cell called microtubules, pulling the cargo forward.
The movement of the heads, or motor domains, is fueled by the breakdown of ATP, a molecule that stores the energy that drives cellular work.
When cargo isn't attached, kinesin folds in upon itself to prevent ATP from being squandered.
Although scientists knew that one tail binds to the two heads to keep it in a folded "autoinhibited" state, the molecular mechanism remains unclear.
This research was supported by Cancer Research UK, the National Institutes of Health, the National Science Foundation and Singapore's Agency for Science, Technology and Research.