Scientists determine 3-dimensional structure of cell's 'fuel gauge'

February 8, 2007

Researchers at Columbia University Medical Center have uncovered the complex structure of a protein that serves as a central energy gauge for cells, providing crucial details about the molecule necessary for developing useful new therapies for diabetes and possibly obesity. A paper published online today in the journal Science details this structure, helping to explain one of the cell's most basic and critical processes.

"Understanding this important protein's molecular structure and mechanism provides a major step forward for the rational design of new drugs to target diabetes and obesity," said Lawrence Shapiro, Ph.D., associate professor of Biochemistry and Jules and Doris Stein Professor of Research to Prevent Blindness at Columbia University Medical Center, and senior author of the paper.

The protein, known as AMP-activated protein kinase or AMPK, controls metabolic decisions of cells. For example, it controls the decision regarding whether fat is stored or burned, based on the amount of energy in the cell. When the energy level of a cell is high, meaning that the cell contains high amounts of an energy-carrying molecule known as ATP, AMPK directs cells toward "anabolic" activities like storing the extra energy as fat. When ATP is low, AMPK turns off anabolic activities, and activates "catabolic" functions, like burning fat to make energy.

AMPK provides an especially promising drug target for people with type 2 diabetes. These patients are insulin-resistant, meaning that their cells are not responsive to insulin which normally helps glucose get out of the bloodstream, where it does damage, and into cells. When AMPK detects low levels of ATP in the cell, it works through a different mechanism to increase how much glucose the cell takes in and uses to create ATP. Research in rodent models has shown that AMPK activators can lessen the pathologies associated with diabetes, including problems that diabetics have regulating blood sugar.

Dr. Shapiro explained that researchers do not yet know how to activate AMPK without activating other proteins and causing potentially toxic side effects. However, he notes that this development in understanding the atomic resolution structure of the protein provides researchers a powerful new tool for the design of useful therapeutics.

Source: Columbia University Medical Center

Explore further: Manipulating mitochondrial networks could promote healthy aging

Related Stories

Manipulating mitochondrial networks could promote healthy aging

October 26, 2017
Manipulating mitochondrial networks inside cells—either by dietary restriction or by genetic manipulation that mimics it—may increase lifespan and promote health, according to new research from Harvard T.H. Chan School ...

Scientists uncover how a cell's 'fuel gauge' promotes healthy development

April 25, 2016
Salk scientists have revealed how a cellular "fuel gauge" responsible for monitoring and managing cells' energy processes also has an unexpected role in development. This critical link could help researchers better understand ...

Researchers uncover signal that switches cells to cancerous metabolism

February 11, 2015
Abnormal metabolism within the cells is a distinctive characteristic of cancer, but until now, the mechanism that causes cells to undergo this metabolic shift remained unknown.

New study shows inhibiting copper chaperones reduces tumor cell proliferation

November 20, 2015
(Phys.org)—Researchers from several institutions have found that copper trafficking chaperones are a good target for suppressing tumor growth without affecting healthy cells.

Study finds mechanism that regulates lung function in disease Birt-Hogg-Dube syndrome

April 10, 2014
Researchers at Penn Medicine have discovered that the tumor suppressor gene folliculin (FLCN) is essential to normal lung function in patients with the rare disease Birt-Hogg-Dube (BHD) syndrome, a genetic disorder that affects ...

'Hunger' neurons in the brain are regulated by protein activated during fasting

July 6, 2016
Neurons in the brain that control hunger are regulated by AMPK, a protein activated during fasting, report researchers from Tufts University School of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School ...

Recommended for you

Scientists find key to regenerating blood vessels

November 23, 2017
A new study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) identifies a signaling pathway that is essential for angiogenesis, the growth of new blood vessels from pre-existing vessels. The ...

Researchers find infectious prions in Creutzfeldt-Jakob disease patient skin

November 22, 2017
Creutzfeldt-Jakob disease (CJD)—the human equivalent of mad cow disease—is caused by rogue, misfolded protein aggregates termed prions, which are infectious and cause fatal damages in the patient's brain. CJD patients ...

Surprising roles for muscle in tissue regeneration, study finds

November 22, 2017
A team of researchers at Whitehead has illuminated an important role for different subtypes of muscle cells in orchestrating the process of tissue regeneration. In a paper published in the November 22 issue of Nature, they ...

Study reveals new mechanisms of cell death in neurodegenerative disorders

November 22, 2017
Researchers at King's College London have discovered new mechanisms of cell death, which may be involved in debilitating neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.

How rogue immune cells cross the blood-brain barrier to cause multiple sclerosis

November 21, 2017
Drug designers working on therapeutics against multiple sclerosis should focus on blocking two distinct ways rogue immune cells attack healthy neurons, according to a new study in the journal Cell Reports.

New simple test could help cystic fibrosis patients find best treatment

November 21, 2017
Several cutting-edge treatments have become available in recent years to correct the debilitating chronic lung congestion associated with cystic fibrosis. While the new drugs are life-changing for some patients, they do not ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.