High density lipoprotein (HDL) has been proposed to be a major mediator of the transport of excess cholesterol from peripheral cells to the liver for clearance from the body. Recent reports have indicated that some subspecies of HDL may have an enhanced ability to perform this function. The most common apolipoprotein in HDL, apolipoprotein (apo) Al, appears to modulate the structure of HDL as well as its interaction with various plasma factors. However, the structure of the apo Al is not yet known in detail. The proposed research will utilize specific apoAl variants produced by site-directed and deletional mutagenesis. The abilities of these variants to self-associate, bind lipid, and form reconstituted HDL particles will be determined. The structure of the variants in both the lipid-free and -bound forms will be probed by circular dichroism and fluorescence techniques. The results from these studies will provide information on the relative abilities of the various domains in apoAl to bind lipid and to interact with other apolipoproteins. In addition, specific information will be obtained on the chemical environments of individual tryptophan residues in the N-terminal region of apoAl.
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