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

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