Elevated levels of serum low density lipoprotein (LDL) are an established atherogenic factor, hat promotes cholesteryl ester accumulation in the arterial wall. The detailed structure of the LDL is not known. The generally accepted model is the following. The neutral lipids, cholesterol ester and triglycerides, form a lipid core that is surrounded by the surface components phospholipids (PL), cholesterol and the amphipathic apolipoprotein B-100 (apoB-100). ApoB100 is a 4536 amino acid glycoprotein which functions as the ligand for binding LDL to its cell surface receptor, the essential processes for removing LDL from the circulation. Studies of the structure of human low-density lipoprotein subfractions, determined by X-ray small-angle scattering, do not support radial symmetry or a globular structure, but implies a spread-out conformation of the apolipoprotein B (apoB) molecule, which appears to be localized in the outer surface shell. Direct observation of LDL in ice by electron image analysis is intended to solve the structure of LDL. Images of ice-embedded individual molecules of LDL in the presence of plasma levels of sodium cholate have been taken at 400 keV. They show the molecule in different orientations as 'barrels' of about 250x200 _. Many of them show characteristic bands, or stripes spanning the interior of the barrel. Those stripes possibly represent the lipid bilayers present in LDL. To provide a structural marker on LDL to facilitate orientation of individual LDL molecules for image processing, a mouse monoclonal antibody to LDL, purified by affinity chromatography over an LDL-Sepharose column, was mixed with LDL before visualization in ice. Initial studies show a high proportion of LDL:antibody complexes. These preliminary results suggest this experimental approach may be useful in determining the structure of LDL.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR002250-11
Application #
5223867
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
1996
Total Cost
Indirect Cost
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