PMID- 21821149
OWN - NLM
STAT- MEDLINE
DCOM- 20121126
LR  - 20181201
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1821
IP  - 3
DP  - 2012 Mar
TI  - Identification of an amino acid residue in ATP-binding cassette transport G1 
      critical for mediating cholesterol efflux.
PG  - 552-9
LID - 10.1016/j.bbalip.2011.07.012 [doi]
AB  - The ATP-binding cassette transporter G1 (ABCG1) mediates free cholesterol efflux 
      onto lipidated apolipoprotein A-I (apoA-I) and plays an important role in 
      macrophage reverse cholesterol transport thereby reducing atherosclerosis. 
      However, how ABCG1 mediates the efflux of cholesterol onto lipidated apoA-I is 
      unclear. Since the crystal structure of ABCG family is not available, other 
      approaches such as site-directed mutagenesis have been widely used to identify 
      amino acid residues important for protein functions. We noticed that ABCG1 
      contains a single cysteine residue in its putative transmembrane domains. This 
      cysteine residue locates at position 514 (Cys(514)) within the third putative 
      transmembrane domain and is highly conserved. Replacement of Cys(514) with Ala 
      (C514A) essentially abolished ABCG1-mediated cholesterol efflux onto lipidated 
      apoA-I. Substitution of Cys(514) with more conserved amino acid residues, Ser or 
      Thr, also significantly decreased cholesterol efflux. However, mutation C514A had 
      no detectable effect on protein stability and trafficking. Mutation C514A also 
      did not affect the dimerization of ABCG1. Our findings demonstrated that the 
      sulfhydryl group of Cys residue located at position 514 plays a critical role in 
      ABCG1-mediated cholesterol efflux. This article is part of a Special Issue 
      entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute 
      to John F. Oram (1945-2010).
CI  - Copyright A(c) 2011 Elsevier B.V. All rights reserved.
FAU - Gao, Xia
AU  - Gao X
AD  - Department of Pediatrics and Group on the Molecular and Cell Biology of Lipids, 
      University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
FAU - Gu, Hongmei
AU  - Gu H
FAU - Li, Ge
AU  - Li G
FAU - Rye, Kerry-Anne
AU  - Rye KA
FAU - Zhang, Da-Wei
AU  - Zhang DW
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110729
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (ABCG1 protein, human)
RN  - 0 (APOA1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Apolipoprotein A-I)
RN  - 139873-08-8 (Calnexin)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - K848JZ4886 (Cysteine)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1
MH  - ATP-Binding Cassette Transporters/*genetics/isolation & purification/metabolism
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Apolipoprotein A-I/metabolism
MH  - Calnexin/metabolism
MH  - Cholesterol/*metabolism
MH  - Chromatography, Gel
MH  - Conserved Sequence
MH  - Cysteine/*genetics
MH  - HEK293 Cells
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Protein Multimerization
MH  - Protein Structure, Quaternary
MH  - Protein Transport
EDAT- 2011/08/09 06:00
MHDA- 2012/12/10 06:00
CRDT- 2011/08/09 06:00
PHST- 2011/04/29 00:00 [received]
PHST- 2011/07/07 00:00 [revised]
PHST- 2011/07/15 00:00 [accepted]
PHST- 2011/08/09 06:00 [entrez]
PHST- 2011/08/09 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - S1388-1981(11)00137-5 [pii]
AID - 10.1016/j.bbalip.2011.07.012 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2012 Mar;1821(3):552-9. doi: 10.1016/j.bbalip.2011.07.012. 
      Epub 2011 Jul 29.