Featured Research

from universities, journals, and other organizations

Scientists discover how molecular motors go into 'energy save mode'

Date:
August 11, 2011
Source:
Carnegie Mellon University
Summary:
The transport system inside living cells is a well-oiled machine with tiny protein motors hauling vital cargo around the cell. A new study describes how the motors save energy, when their transport services aren't required. The solution to this molecular puzzle provides new insight into how molecular motor proteins are regulated, and may open new avenues for the treatment of various neurodegenerative diseases, such as Alzheimer's and Huntington's.

Structural rendering of kinesin’s two heads, called motor domains, cross-linked by a bound tail domain (green).
Credit: Image courtesy of Carnegie Mellon University

The transport system inside living cells is a well-oiled machine with tiny protein motors hauling chromosomes, neurotransmitters and other vital cargo around the cell. These molecular motors are responsible for a variety of critical transport jobs, but they are not always on the go. They can put themselves into "energy save mode" to conserve cellular fuel and, as a consequence, control what gets moved around the cell, and when.

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, and 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. Several possibilities have been proposed, but these latest findings suggest only one solution.

Hackney worked with Hung Yi Kristal Kaan and Frank Kozielski at the Beatson Institute for Cancer Research in Glasgow, Scotland, who crystallized a key portion of the kinesin molecule -- a tail that was bound to the heads. The crystal structure confirmed that the complex contained two head domains and only one tail domain. Hackney then carried out biochemical manipulations to determine precisely how the tail interacts with the heads, which turned out to be what the authors refer to as a "double lockdown."

"It was actually a big surprise," Hackney said, "because it ruled out all of the obvious things that had been proposed for how the tail domain autoinhibits the motor domain. It does not cause a conformational change, and it does not block the surfaces that interact with ATP or the microtubular track."

Kinesin's heads are typically joined together at one spot, called the hinge. In the new structure, the heads swing in toward each other and are bridged by the tail domain, effectively cross-linking the heads at the site of tail binding. This double lockdown -- at the hinge and at the bridge -- prevents the heads from separating. Because the heads need to be separate from each other to break down ATP, the double lockdown effectively stops the molecule from generating fuel to power the motor.

The researchers suggest that other kinesins may be regulated by the same autoinhibitory mechanism. Humans have dozens of different kinesin motors that transport a variety of cargo, including proteins associated with Alzheimer's, Huntington's and Parkinson's diseases. Kinesins are also involved in separating chromosomes during cell division, making the motors a target for cancer therapies that seek to stop the motors from transporting chromosomes, which would prevent cancer cells from multiplying.

This research was supported by Cancer Research UK, the National Institutes of Health, the National Science Foundation andSingapore's Agency for Science, Technology and Research.


Story Source:

The above story is based on materials provided by Carnegie Mellon University. Note: Materials may be edited for content and length.


Journal Reference:

  1. H. Y. K. Kaan, D. D. Hackney, F. Kozielski. The Structure of the Kinesin-1 Motor-Tail Complex Reveals the Mechanism of Autoinhibition. Science, 2011; 333 (6044): 883 DOI: 10.1126/science.1204824

Cite This Page:

Carnegie Mellon University. "Scientists discover how molecular motors go into 'energy save mode'." ScienceDaily. ScienceDaily, 11 August 2011. <www.sciencedaily.com/releases/2011/08/110811151318.htm>.
Carnegie Mellon University. (2011, August 11). Scientists discover how molecular motors go into 'energy save mode'. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2011/08/110811151318.htm
Carnegie Mellon University. "Scientists discover how molecular motors go into 'energy save mode'." ScienceDaily. www.sciencedaily.com/releases/2011/08/110811151318.htm (accessed October 21, 2014).

Share This



More Plants & Animals News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

'Cadaver Dog' Sniffs out Human Remains

'Cadaver Dog' Sniffs out Human Remains

AP (Oct. 21, 2014) Where's a body buried? Buster's nose can often tell you. He's a cadaver dog, specially trained to find human remains and increasingly being used by law enforcement and accepted in courts. These dogs are helping solve even decades-old mysteries. (Oct. 21) Video provided by AP
Powered by NewsLook.com
White Lion Cubs Born in Belgrade Zoo

White Lion Cubs Born in Belgrade Zoo

AFP (Oct. 20, 2014) Two white lion cubs, an extremely rare subspecies of the African lion, were recently born at Belgrade Zoo. They are being bottle fed by zoo keepers after they were rejected by their mother after birth. Duration: 00:42 Video provided by AFP
Powered by NewsLook.com
Traditional Farming Methods Gaining Ground in Mali

Traditional Farming Methods Gaining Ground in Mali

AFP (Oct. 20, 2014) He is leading a one man agricultural revolution in Mali - Oumar Diatabe uses traditional farming methods to get the most out of his land and is teaching others across the country how to do the same. Duration: 01:44 Video provided by AFP
Powered by NewsLook.com
Goliath Spider Will Give You Nightmares

Goliath Spider Will Give You Nightmares

Buzz60 (Oct. 20, 2014) An entomologist stumbled upon a South American Goliath Birdeater. With a name like that, you know it's a terrifying creepy crawler. Sean Dowling (@SeanDowlingTV) has the details. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins