{"id":{"repo_id":"wfu","oai_identifier":"oai:wakespace.lib.wfu.edu:10339/57096"},"canonical_url":"https://search.dev.ndltd.org/etd/wfu/oai:wakespace.lib.wfu.edu:10339/57096","repository":{"repo_id":"wfu","name":"Wake Forest University","base_url":"https://wakespace.lib.wfu.edu/oai/request"},"display":{"title":"The Role of Lipid-Free Apolipoprotein A-I and PCPE2 in HDL Metabolism","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Pollard, Ricquita DeAnn"],"institution":"Wake Forest University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015","date_published":"2015","updated_at":"2026-07-27T22:01:52Z","subjects":["ApoA-I"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10339/57096","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Pollard, Ricquita DeAnn"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2015-06-23T08:35:33Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2015-06-23T08:35:33Z"]},{"key":"dc:date.issued","label":"Date","values":["2015"]},{"key":"dc:publisher","label":"Institution","values":["Wake Forest University"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["ApoA-I"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10339/57096"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:title","label":"Title","values":["The Role of Lipid-Free Apolipoprotein A-I and PCPE2 in HDL Metabolism"]}]}],"canonical_facts":{"dc:creator":["Pollard, Ricquita DeAnn"],"dc:date.accessioned":["2015-06-23T08:35:33Z"],"dc:date.available":["2015-06-23T08:35:33Z"],"dc:date.issued":["2015"],"dc:description.abstract":["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."],"dc:identifier.uri":["http://hdl.handle.net/10339/57096"],"dc:language.iso":["en"],"dc:publisher":["Wake Forest University"],"dc:subject":["ApoA-I"],"dc:title":["The Role of Lipid-Free Apolipoprotein A-I and PCPE2 in HDL Metabolism"],"dc:type":["Dissertation"]},"updated_at":"2026-07-27T22:01:52Z"}