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:12/2/2016)... ... December 02, 2016 , ... U.S. Surgeon General, Dr. Vivek ... Dr. Murthy explains how he was inspired to practice medicine at an early age ... is about more than making diagnoses and prescribing medicine,” he states. “It is about ...
(Date:12/2/2016)... ... December 02, 2016 , ... Dr. Raffi Hovsepian, a leading ... the 2016 “Guide to America’s Top Plastic Surgeons” for seven consecutive years. The ... education, experience, and professional associations. , One the most frequently honored surgeons ...
(Date:12/2/2016)... ... December 02, 2016 , ... ... of its SaaS LIMS, CloudLIMS Lite. CloudLIMS Lite helps biobanks, clinical, research and ... storing, shipping and disposal. The new version is a faster and a more ...
(Date:12/2/2016)... (PRWEB) , ... December 02, 2016 , ... Sourced from ... has some unique properties including its unmatched natural purity of just 6 ppm TDS ... and crisp. , Nothing Water has been available in several ShopRite and FoodTown stores ...
(Date:12/2/2016)... ... December 02, 2016 , ... "Pro3rd Accents Volume 2 is ... create versatile lower third titles with just a few clicks of the mouse," said ... includes 30 lower third animations. Choose from various styles with accented animations, rigid boxes, ...
Breaking Medicine News(10 mins):
(Date:12/2/2016)... , December 2, 2016 According ... titled "Global Market Study on Automated Endoscope Reprocessors: Single Basin ... CAGR of 8.6% Between 2016 and 2024 " the global automated endoscope ... is expected to expand at a CAGR of 7.2% during ... of US$ 1,367.6 Mn by 2024. ...
(Date:12/2/2016)... ATLANTA , Dec. 2, 2016 Quantum ... screening and expert radiologist interpretation directly to women at ... partners with corporations, such as Delta Air Lines and ... cancer screening as a component of wellness initiatives. ... women of SunTrust. It enables them to have a ...
(Date:12/2/2016)... , December 2, 2016 ... Awards Committee honored excellence in research, development and innovation ... The gala dinner was held in the presence of ... the Russian Federation , Natalia Sanina, ... Mikhail Murashko , Head of Roszdravnadzor, National Service ...
Breaking Medicine Technology: