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LOW DENSITY LIPOPROTEIN

$0P41FY2001RRNIH

Baylor College Of Medicine, Houston TX

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Abstract

Low density lipoproteins (LDL) are the major cholesterol transporters in the blood circulation. LDL are the end stage particles resulting from the metabolism of very low density lipoproteins (VLDL) and they stay in the blood circulation for 2-3 days until being taken up by liver. LDL contain apolipoprotein apoB-100 which is one of the largest proteins known (4536 amino acids). Very little is known about the three-dimensional structure of LDL. According to existing hypotheses, LDL are simply microemulsions with a non-polar core and an outside shell which provides the water solubility for the particle. The shell is formed by the amphipathic apolipoprotein and phospholipids. Elevated levels of VLDL, LDL and apo B-100 are associated with a significantly increased risk of coronary arteriosclerosis and heart attack. We used electron cryomicroscopy of ice-embedded LDL and computer image processing to study their three-dimensional structure We proposed, based on three-dimensional reconstruction, that LDL are not structureless, easily deformable lipid sacks as was commonly believed. Rather, they have an oval shape and a consistent internal structure. The particle s core has a stable structure consisting of several compartments. Its outer shell most probably consists of apolipoprotein B-100 and phospholipids and the core compartmentalization might correspond to either ordered lipids, or protein intrusions. To distinguish between the two hypotheses further study is needed.

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