2026-09-21T05:55:59Zhttps://wakespace.lib.wfu.edu/server/oai/request

oai:null:10339/570962026-09-02T16:23:03Zcom_10339_14934col_10339_38132

Pollard, Ricquita DeAnn 2015-06-23T08:35:33Z 2015-06-23T08:35:33Z 2015 https://wakespace.lib.wfu.edu/handle/10339/57096 The purpose of this work is to investigate the role of apolipoprotein apoA-I (apoA-I) and procollagen C-endopeptidase enhancer 2 (PCPE2) in high density lipoprotein (HDL) metabolism. ApoA-I comprises ~70 percent of the protein within HDL and has an essential role in cholesterol efflux from peripheral cells as part of the reverse cholesterol transport pathway. Lipid-free apoA-I undergoes conformational changes as HDL is formed, a poorly understood mechanism. We determined the structure of lipid-free apoA-I based on chemical cross-linking in conjunction with disulfide cross-linking to define distance constraints. Results indicate lipid-free apoA-I is compact with amino acids 44-186 bundled together with the N-and C-terminal ends folded so that they lie close to one another. We tested the accuracy of our model by determining the distance between two residues by engineering cysteine mutant apoA-I designed to “lock” or “unlock” by being within or exceeding 3-5 Å, respectively. These mutant apoA-I were used to assess the opening mechanism for lipid-free apoA-I lipidation to form recombinant HDL (rHDL) and nascent HDL (nHDL). Results of these studies identify central helices 4-6 as essential for rHDL and nHDL formation. en Wake Forest University ApoA-I Atherosclerosis HDL PCPE2 The Role of Lipid-Free Apolipoprotein A-I and PCPE2 in HDL Metabolism Dissertation Sorci-Thomas, Mary G. Lowther, W. Todd Hantgan, Roy R Parks, John S Thomas, Michael J Molecular Pathology open.access