Navigation Links
Carnegie Mellon scientists discover how molecular motors go into 'energy save mode'

PITTSBURGHThe 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 from Carnegie Mellon University and the Beatson Institute for Cancer Research 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.


Contact: Jocelyn Duffy
Carnegie Mellon University

Related biology news :

1. Carnegie Mellons Matyjaszewski to receive Wolf Prize in Chemistry
2. Carnegie Mellon researchers identify Facebook neurons
3. Carnegie Mellon researchers discover mechanism for signaling receptor recycling
4. Carnegie Mellon receives funding to create new program studying environmental impact of nanotechnology
5. Carnegie Mellon hosting first conference to explore scientific use of gigapixel imagery
6. Neuronal diversity makes a difference, says Carnegie Mellon study
7. Carnegie Mellon researchers turn up brightness on fluorescent probes
8. Carnegie Mellons Yoed Rabin receives grants
9. Carnegie Mellon researchers create fluorescent biosensor to aid in drug development
10. Carnegies Doug Koshland elected to National Academy of Sciences
11. Carnegies Chris Field elected to American Academy of Arts & Sciences
Post Your Comments:
Related Image:
Carnegie Mellon scientists discover how molecular motors go into 'energy save mode'
(Date:6/20/2016)... Securus Technologies, a leading provider of ... safety, investigation, corrections and monitoring announced that after ... secured the final acceptance by all three (3) ... Systems (MAS) installed. Furthermore, Securus will have contracts ... by October, 2016. MAS distinguishes between legitimate wireless ...
(Date:6/7/2016)... June 7, 2016  Syngrafii Inc. and San ... relationship that includes integrating Syngrafii,s patented LongPen™ eSignature ... This collaboration will result in greater convenience for ... union, while maintaining existing document workflow and compliance ... ...
(Date:6/1/2016)... NEW YORK , June 1, 2016 ... Biometric Technology in Election Administration and Criminal Identification to ... According to a recently released TechSci Research report, " ... Sector, By Region, Competition Forecast and Opportunities, 2011 - ... $ 24.8 billion by 2021, on account of growing ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... , June 24, 2016 Epic Sciences ... detects cancers susceptible to PARP inhibitors by targeting ... cells (CTCs). The new test has already been ... in multiple cancer types. Over 230 ... damage response pathways, including PARP, ATM, ATR, DNA-PK ...
(Date:6/23/2016)... June 23, 2016   Boston Biomedical , ... compounds designed to target cancer stemness pathways, announced ... granted Orphan Drug Designation from the U.S. Food ... gastric cancer, including gastroesophageal junction (GEJ) cancer. Napabucasin ... to inhibit cancer stemness pathways by targeting STAT3, ...
(Date:6/23/2016)... Prostate Cancer Foundation (PCF) is pleased to announce 24 new Young Investigator ... Members of the Class of 2016 were selected from a pool of 128 ... About the Class of 2016 PCF Young Investigators ... ... ...
(Date:6/23/2016)... Durham, NC (PRWEB) , ... June 23, 2016 , ... ... Odense University Hospital in Denmark detail how a patient who developed lymphedema after being ... (fat) tissue. The results could change the paradigm for dealing with this debilitating, frequent ...
Breaking Biology Technology: