Navigation Links
Researchers identify structure of apolipoprotein
Date:11/4/2011

(Boston) - Using a sophisticated technique of x-ray crystallography, researchers Xiaohu Mei, PhD, and David Atkinson, PhD, from Boston University School of Medicine (BUSM) have for the first time obtained an "image" of the structure and the precise arrangement of the atoms in a truncated form of the apolipoprotein A-I (apoA-I) molecule. The findings, which appear in the November issue of the Journal of Biological Chemistry, may lead to the development of new drugs to treat obesity, stroke and diabetes.

Errors in the regulation of the metabolism and transport of fats in the body are the number one cause of death and morbidity in the United States and most parts of the world. These problems are exemplified by the prevalence of diseases such as atherosclerosis, cardiovascular disease and stroke.

High blood levels of HDL or "good cholesterol" protect against atherosclerosis and cardiovascular disease. This protection is related HDL's role to remove cholesterol from cells in the tissues of the body. The major protein of HDL is called apoA-I. ApoA-I solubilizes fats and cholesterol and builds the HDL particle. ApoA-I plays important roles in the process of cholesterol removal by HDL.

ApoA-I interacts with another protein in the membrane of cells called the ABCA1 transporter, and removes cholesterol from the cells to form a "nascent" HDL particle.

In the blood, apoA-I in the nascent HDL activates the enzyme, lecithin-cholesterol acyltransferase (LCAT), which results in the solubilization of more cholesterol and the formation of a "mature" HDL particle. This HDL particle is transported in the blood stream to the liver where apoA-I binds to yet another cell membrane protein (hepatic SR-B1 receptor) and cholesterol is delivered to the liver and can be excreted from the body.

"Despite this central role in fat and cholesterol transport and metabolism, a detailed molecular understanding of apoA-I and how apoA-I forms an HDL particle have remained enigmatic for more than three decades," said study author David Atkinson, PhD, chairman and professor of physiology and Biophysics at BUSM as well as a research professor of biochemistry.

"The structure shows the precise molecular and atomic details of how two molecules of apoA-I bind to each other to form a half circle arrangement that can solubilize fatty molecules and cholesterol to form the "nascent" HDL. In addition, the structure suggests how a central section of the protein may form a tunnel through which cholesterol can be moved during the interaction with LCAT. Finally, the structure provides the molecular details that may underlie the structural and functional effects of important apoA-I mutations that cause abnormalities in HDL function," he explained.

According to the researcher, understanding, in molecular detail, the processes of fat and cholesterol transport, cellular uptake and removal is crucial to understanding how these processes occur in the healthy state and become dysregulated in diseases such as atherosclerosis. "With the mechanistic insights provided by this knowledge, new drugs may be developed to regulate and treat human diseases including obesity, atherosclerosis, stroke metabolic syndrome and the dyslipidemia associated with diabetes," added Atkinson.


'/>"/>

Contact: Gina DiGravio
gina.digravio@bmc.org
617-638-8480
Boston University Medical Center
Source:Eurekalert

Related medicine news :

1. Researchers map all the fragile sites of the yeast Saccharomyces cerevisiaes genome
2. UH Case Medical Center researchers publish promising findings for advanced cervical cancer
3. Researchers discover new way to kill pediatric brain tumors
4. Researchers Who Discovered First Genes for Stuttering will Present Findings to the National Stuttering Association
5. Researchers create drug to keep tumor growth switched off
6. Urine protein test might help diagnose kidney damage from lupus, UT Southwestern researchers find
7. GUMC researchers say flower power may reduce resistance to breast cancer drug tamoxifen
8. Clemson researchers develop hands-free texting application
9. Researchers find biomarkers in saliva for detection of early-stage pancreatic cancer
10. Researchers chart genomic map spanning over 2 dozen cancers
11. Researchers discover second protective role for tumor-suppressor
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/24/2016)... ... May 24, 2016 , ... United Benefit Advisors (UBA), ... Partner Firm Austin & Co., Inc. Headquartered in Albany, New York, Austin ... consulting, benefits technology, and beyond. As an employee-owned company celebrating over 160 ...
(Date:5/24/2016)... VA (PRWEB) , ... May 24, 2016 , ... ... for the Surgery Center at Sentara Northern Virginia Medical Center located in Woodbridge, ... of the hospital’s surgical services into a single site. , The new 2 ...
(Date:5/24/2016)... ... 2016 , ... Mental health watchdog Citizens Commission on Human Rights (CCHR) ... of psychiatry Thomas Szasz, is continuing its protest against the use of electroshock (ECT) ... Atlanta, Georgia. The opening of the exhibit follows CCHR’s recent protest at the annual ...
(Date:5/24/2016)... ... May 24, 2016 , ... Loma Linda University Health (LLUH) has officially ... expanded Children’s Hospital. Over 3,000 people looked on as the shovels hit the dirt ... photo slidehsow. , During the program, Richard H. Hart, MD, DrPH, president, LLUH, ...
(Date:5/24/2016)... ... , ... Backed by decades of experience, Metroloji Okulu works ... best suited solution to meet regulatory requirements. Their professional staff also performs on-site ... , Metroloji Okulu specializes in MadgeTech’s line of medical and pharmaceutical data ...
Breaking Medicine News(10 mins):
(Date:5/24/2016)... HONG KONG , May 24, 2016 ... , the world , s ... and AV fistula intervention   OrbusNeich, a ... solutions, has expanded its portfolio to include products to ... balloons are the company,s first entry devices for lower ...
(Date:5/24/2016)... 2016 Les ... la première endoprothèse à double thérapie au ... portant sur les membres inférieurs et la ... entreprise mondiale spécialisée dans la fourniture de ... a élargi son portefeuille pour inclure des ...
(Date:5/24/2016)... May 24, 2016 Dutch surgeons have launched ... around the world and treat patients on a global scale. Medical ... , Asia and the US have already ... messaging and networking in a totally secure environment. Education  ... war zone working together with a surgeon at Harvard to treat ...
Breaking Medicine Technology: