IDEALS Home University of Illinois at Urbana-Champaign logo The Alma Mater The Main Quad

Structure and function studies on five homogeneous reconstituted HDL complexes

Show full item record

Bookmark or cite this item: http://hdl.handle.net/2142/19445

Files in this item

File Description Format
PDF 9114262.pdf (7MB) Restricted to U of Illinois (no description provided) PDF
Title: Structure and function studies on five homogeneous reconstituted HDL complexes
Author(s): Hefele Wald, Jennifer Elaine
Doctoral Committee Chair(s): Jonas, Ana
Department / Program: Biochemistry
Discipline: Biochemistry
Degree Granting Institution: University of Illinois at Urbana-Champaign
Degree: Ph.D.
Genre: Dissertation
Subject(s): Chemistry, Biochemistry Health Sciences, Medicine and Surgery
Abstract: High density lipoprotein (HDL) is believed to be involved in reverse cholesterol transport. HDL consists primarily of phospholipids, cholesterol, cholesterol esters, and apolipoprotein A-I (apo A-I). However, HDL is extremely heterogeneous in size composition and the structure of its lipoprotein components, particularly apo A-I. Due to its inherent structural heterogeneity, structure-function studies on native HDL have been extremely difficult. Techniques were thus developed to reconstitute HDL (rHDL) from apolipoproteins and pure lipids. These rHDL have been heterogeneous in size and the number of apo A-I molecules per complex. This work shows the isolation of 5 rHDL complexes to homogeneity, and the results of studies of rHDL, apo A-I, and lipid structure in these rHDL. Furthermore, the reactivity of these complexes with lecithin cholesterol acyltransferase (LCAT) was also investigated. The rHDL structures were investigated by assays for chemical composition; and the dimensions were determined by native gel electrophoresis and electron microscopy. The protein structure was studied by a variety of fluorescence techniques, and circular dichroism, and infrared spectroscopies. Monoclonal antibody studies, trypsinolysis and structural algorithmic studies were also employed to probe the protein structure. The lipid structure was studied by infrared spectroscopy, and with lipophilic fluorescent probes. Kinetic studies of the complexes were performed with LCAT. This work shows that apo A-I not only has a different structure in the lipid bound versus the lipid free state, but that it has distinct and reproducible structures in the lipid bound state. The alpha helices of apo A-I run parallel to the lipid acyl chains in the discoidal rHDL. The lipid dynamics are affected by both the lipid and protein composition of the complexes; and, differences in rHDL reactivity with LCAT are correlated to differences in lipid content, and apo A-I and rHDL structure.
Issue Date: 1990
Type: Text
Language: English
URI: http://hdl.handle.net/2142/19445
Rights Information: Copyright 1990 Hefele Wald, Jennifer Elaine
Date Available in IDEALS: 2011-05-07
Identifier in Online Catalog: AAI9114262
OCLC Identifier: (UMI)AAI9114262
 

This item appears in the following Collection(s)

Show full item record

Item Statistics

  • Total Downloads: 0
  • Downloads this Month: 0
  • Downloads Today: 0

Browse

My Account

Information

Access Key