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Biochemical Characterization of ATP-Binding Cassette Transporter G1 Mediated Cholesterol Efflux Open Access
- Other title
- Type of item
- Degree grantor
University of Alberta
- Author or creator
- Supervisor and department
Zhang, Dawei (Medical Sciences--Paediatrics)
- Examining committee member and department
Berthiaume, Luc (Cell Biology)
Lehner, Richard (Cell Biology and Medical Sciences--Paediatrics)
Zhang, Dawei (Paediatrics)
- Date accepted
- Graduation date
Master of Science
- Degree level
ABCG1 mediates cholesterol efflux onto lipidated apolipoprotein A-I and plays an important role in macrophage reverse cholesterol transport, thereby preventing atherosclerosis. However, how ABCG1 mediates cholesterol efflux is unclear.
We found that Cys514 located within the third putative transmembrane domain is highly conserved. Replacement of Cys514 with Ala abolished ABCG1-mediated cholesterol efflux. Substitution of Cys514 with the more conserved amino acid, Ser or Thr, also significantly decreased cholesterol efflux. However, mutation C514A had no effect on ABCG1 stability, trafficking to plasma membrane or its dimerization.
Given the hydrophobicity of cholesterol and the abundance of cysteines, we proposed that ABCG1 is S-palmitoylated. Indeed, ABCG1 is S-palmitoylated at multiple N-terminal cysteines, but they are not functionally equivalent. Mutation at Cys311 dramatically impaired ABCG1-mediated cholesterol efflux, whereas mutations at other palmitoylation sites had minor or no effect. Moreover, defective palmitoylation had no effect on protein stability, trafficking, distribution pattern or the dimerization.
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- Citation for previous publication
Gao, X., Gu, H., Li, G., Rye, K. A., and Zhang, D. W. (2011) Biochim Biophys Acta, In press
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