Navigation Links
Key heart and Alzheimer's disease protein imaged for first time in native state

Researchers for the first time have created a three-dimensional image of apolipoprotein E, a protein long associated with cardiovascular disease and more recently with Alzheimer's disease, as it appears when it is bound to fat-like substances known as lipids.

Using the technique known as x-ray crystallography, scientists at the Gladstone Institute of Cardiovascular Disease (GICD) have created the highest-resolution x-ray structure of a lipoprotein particle to date.

The work focuses apoE4, one of three specific forms of apolipoprotein E, commonly known as apoE. The breakthrough has already answered long-standing questions about the configuration of apoE4 in its active, or native, state. A complete understanding of the protein's functioning will be a key factor for development of future therapeutic interventions, according to the researchers.

Details of the works are reported in the January 13 edition of the Journal of Biological Chemistry.

"This is the first successful use of x-ray crystallography to reveal the structure of a protein bound to lipids," explains senior author Karl Weisgraber, PhD, a senior investigator at both GICD and the Gladstone Institute of Neurological Disease (GIND). "It's crucial to understand this molecule, since it plays such a pivotal role in both cardiovascular and neurological disease.

X-ray crystallography is a technique for determining the three-dimensional structure of a molecule by analyzing the x-ray diffraction patterns of crystals that make up the molecule.

"The next step is higher resolution, going from the current 10 angstroms to 3.5 or better," adds Weisgraber, who is also a professor of pathology at the University of California, San Francisco.

Lipid-bound proteins change their shape once they've bound to a lipid and have begun their key functions. "Until now, we've only been able to model the lipid-free structures of these proteins, and now we can begin learning about their lipid-bound forms," says lead author Clare Peters-Libeu, a GICD and GIND research scientist. "It's a huge step forward for those of us involved in the field."

ApoE, and particularly apoE4, has long been studied for its role as a lipid transport protein and its involvement in cardiovascular disease. Much of the pioneering work on this molecule has been done at Gladstone since the institutes' founding in 1979, led by researchers, including Weisgraber, who had been studying the protein at the National Institutes of Health before transitioning to Gladstone.

In the late 1980s, apoE emerged as a major player in neurological disease, based in part on observations made at Gladstone. Next to one's age, the greatest known risk factor for Alzheimer's disease is the gene for apoE4. ApoE4 is associated with 40-60 percent of cases of sporadic and familial Alzheimer's.

Everyone inherits two copies, or alleles, of every gene, one from each parent, Weisgraber explains. As the number of apoE4 alleles increases from 0 to 2, the risk of AD increases from 20 to 90 percent, and the typical age of onset decreases from 84 years to 68 years. The presence of one apoE4 allele results in an estimated 45 percent chance of developing Alzheimer's by 85 years of age. With two apoE4 alleles, the risk increases to 50?0 percent.

"Insights into the basic biology of apoE--and particularly apoE4--gained by Gladstone scientists have been invaluable in the study of Alzheimer's disease," says Peters-Libeu. "Gaining a complete, three-dimensional understanding of its configuration in its native, lipid-bound state will inevitably lead to even more insights into its role in cardiovascular and neurological disease in the years to come."


Source:Gladstone Institutes

Related biology news :

1. UCSD team discovers specialized, rare heart stem cells in newborns
2. Single stem cells from bone heal a broken heart
3. Python a hearty eater
4. Columbia study shows widely used artery clearing device does not help patients during heart attack
5. Researchers reveal secret of key protein in brain and heart function
6. Stem cell therapy successfully treats heart attack in animals
7. New defibrillator signals doctor of patients irregular heartbeat or device malfunction
8. Survival of heart patients on beta-blockers varies greatly with genetic variation
9. Chemical band-aid prevents heart failure in mice with muscular dystrophy
10. MicroRNA tweaks protein that controls early heart development
11. Ibruprofen and other commonly used painkillers for treating inflammation may increase the risk of heart attack
Post Your Comments:

(Date:9/28/2015)... , Sept. 28, 2015 CLEAR, ... that its expedited traveler service is coming ... transforms travel, bringing a frictionless experience, serious ... "CLEAR offers our travelers an ... service," said Jim Smith , Executive ...
(Date:9/28/2015)... PUNE, India , September 28, 2015 ... Recognition Market by Component (Hardware & Software), Product (Scanner & ... Immigration, Military & Defense, & Others) & Geography Global ... Market is expected to reach USD 3627.90 Million by ... 2020. Browse 65 market data T ...
(Date:9/24/2015)... NEW YORK , Sept. 24, 2015  EyeLock ... will be showcasing its award winning and latest technology ... Anaheim, California . EyeLock,s ... and security with unmatched biometric accuracy, making it the ... DNA.   EyeLock,s platform uses video technology to deliver a ...
Breaking Biology News(10 mins):
(Date:10/9/2015)... On October 8, the Honorable Doris O. ... recognizing the third annual International Plasma Awareness Week (IPAW), ... the Plasma Protein Therapeutics Association (PPTA) and ... , Raise global awareness about plasma donation , ... improving lives , Increase understanding about lifesaving plasma ...
(Date:10/9/2015)... ROCKVILLE, Md. , Oct. 9, 2015 /PRNewswire/ ... developing next generation vaccines based on the LAMP-vax ... an exclusive worldwide licensing agreement with Astellas Pharma ... prevention of any and all allergic diseases in ... will receive an upfront payment of $300 million ...
(Date:10/9/2015)...  Pulmatrix, Inc., (NASDAQ: PULM ) will be webcasting ... th Annual BIO Investor Forum on Tuesday, ... --> th Annual BIO Investor Forum ... pm EDT). --> Pulmatrix will be presenting ... on Thursday, October 15, 2015 at 8:30 am EDT. Additionally, ...
(Date:10/9/2015)... ... October 09, 2015 , ... Leading microbial genomics startup uBiome today launched the ... relationship between weight management and the microbiome. The study uses the ResearchKit framework, designed ... iPhone app. , The uBiome app is available as a free download from the ...
Breaking Biology Technology: