Download the full-sized PDF of Structure and Function Studies of ABCG1Download the full-sized PDF



Permanent link (DOI):


Export to: EndNote  |  Zotero  |  Mendeley


This file is in the following communities:

Graduate Studies and Research, Faculty of


This file is in the following collections:

Theses and Dissertations

Structure and Function Studies of ABCG1 Open Access


Other title
Type of item
Degree grantor
University of Alberta
Author or creator
Li, Ge
Supervisor and department
Zhang, Dawei (Pediatrics)
Examining committee member and department
Lopaschuk, Gary (Pediatrics)
Leslie, Elaine (Physiology)
Lehner, Richard (Pediatrics)
Medical Sciences-Paediatrics

Date accepted
Graduation date
Master of Science
Degree level
ATP-binding cassette transporter G1 (ABCG1) mediates sterol efflux onto lipidated lipoproteins and plays an important role in macrophage cholesterol homeostasis. In this project, we investigated how ABCG1 works as a functional transporter to mediate sterol translocation. First, we found a conserved sequence present in the five ABCG transporter subfamily members. The conserved sequence locates between the nucleotide binding domain and the transmembrane domain and contains five amino acid residues from Asn at position 316 to Phe at position 320 in ABCG1 (NPADF). Detailed mutagenesis study revealed that Asn316 and Phe320 in the conserved sequence played an important role in the regulation of ABCG1 function. We further demonstrated that mutations N316D, N316Q and F320I led to retention of the protein in the endoplasmic reticulum (ER). Thus, the two highly conserved amino acid residues, Asn and Phe, may regulate ABCG1 trafficking, thereby affecting ABCG1-mediated cholesterol efflux. Second, we found a Stat3 binding site (YXXQ) located in the N-terminal cytoplasmic region of ABCG1. Replacement of Tyr at position 157 with Ala essentially eliminated ABCG1-mediated efflux of cholesterol and 7-ketocholesterol. On the other hand, substitution of Gln at position 160 with Ala affected the substrate specificity of ABCG1, reducing 7-ketocholesterol efflux with no significant effect on cholesterol efflux. In summary, we identified residues in the N-terminal cytoplasmic region of ABCG1 important for ABCG1 trafficking, function and substrate specificity.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication

File Details

Date Uploaded
Date Modified
Audit Status
Audits have not yet been run on this file.
File format: pdf (Portable Document Format)
Mime type: application/pdf
File size: 13691901
Last modified: 2015:10:12 16:01:07-06:00
Filename: Li_Ge_Fall 2013.pdf
Original checksum: 7d9718a9149c29c848efbde3382f617e
Well formed: false
Valid: false
Status message: Invalid page dictionary object offset=2335
File title: Microsoft Word - Thesis revision.docx
File author: Ge Li
Activity of users you follow
User Activity Date