ATP-binding cassette transporter A1 contains a novel C-terminal VFVNFA motif that is required for its cholesterol efflux and ApoA-I binding activities.

The Journal of Biological Chemistry
Michael L FitzgeraldMason W Freeman

Abstract

The stimulation of cellular cholesterol and phospholipid efflux by apolipoprotein A-I is mediated by the activity of the ATP-binding cassette transporter A1 (ABCA1). Individuals with Tangier disease harbor loss-of-function mutations in this transporter that have proven useful in illuminating its activity. Here, we analyze a mutation that deletes the last 46 residues of the 2261 amino acid transporter (Delta46) and eliminates its lipid efflux. As the final four amino acids of the C terminus represent a putative PDZ-binding motif, we initially characterized deletion mutants lacking only these residues. Although a moderate decline in lipid efflux was detected, this decline was not as profound as that seen in the Delta46 mutant. Subsequent systematic analysis of the ABCA1 C terminus revealed a novel, highly conserved motif (VFVNFA) that was required for lipid efflux. Alteration of this motif, which is present in some but not all members of the ABCA family, did not prevent trafficking of the transporter to the plasma membrane but did eliminate its binding of apoA-I. Chimeric transporters, generated by substituting the C termini of either ABCA4 or ABCA7 for the endogenous terminus, demonstrated that ABCA1 could stimulate cholesterol ...Continue Reading

References

Aug 15, 1996·Nature·J H Morais CabralR C Liddington
Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Jan 21, 2001·The Journal of Biological Chemistry·O ChambenoitG Chimini
Apr 20, 2001·The Journal of Biological Chemistry·N WangA R Tall
Dec 14, 2001·The Journal of Biological Chemistry·Albert Y Hung, Morgan Sheng
Jun 11, 2002·Biochemical and Biophysical Research Communications·Christa BuechlerGerd Schmitz
Jun 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yong Jiang, Russell F Doolittle
Sep 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Brad Davidson, Michael Levine
Jan 15, 2004·The Journal of Biological Chemistry·Youichi MunehiraKazumitsu Ueda
Feb 6, 2004·Proceedings of the National Academy of Sciences of the United States of America·Klaas VandepoeleYves Van de Peer
Mar 31, 2004·Cellular and Molecular Life Sciences : CMLS·P M Jones, A M George

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Citations

Feb 28, 2006·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Vassilis I ZannisMonty Krieger
Nov 13, 2007·Journal of Bioenergetics and Biomembranes·Robert S Molday
Jul 14, 2009·The Journal of Biological Chemistry·Norimasa TamehiroMichael L Fitzgerald
May 28, 2013·DNA and Cell Biology·Yun-cheng LvChao-ke Tang
Feb 22, 2012·Cardiovascular Research·Sima AllahverdianGordon A Francis
May 27, 2006·American Journal of Respiratory and Critical Care Medicine·Frank BraschGerd Schmitz
May 10, 2006·Clinical Chemistry and Laboratory Medicine : CCLM·Stefania StenirriLaura Cremonesi
Oct 2, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Iris LorenziLucia Rohrer
Mar 20, 2008·Expert Opinion on Therapeutic Targets·Jody T MackKenneth D Tew
Jul 30, 2009·Expert Opinion on Drug Metabolism & Toxicology·Wei Mo, Jian-Ting Zhang
Dec 7, 2010·Trends in Cardiovascular Medicine·Sima Allahverdian, Gordon A Francis
Feb 24, 2009·Biochimica Et Biophysica Acta·Robert S MoldayFaraz Quazi
Jun 27, 2006·Biochimica Et Biophysica Acta·Clara CavelierArnold von Eckardstein
Jan 28, 2015·Biochimica Et Biophysica Acta·Tobias HebelChrista Buechler
Oct 13, 2006·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·J T MackD M Townsend
Jan 31, 2006·Journal of Lipid Research·Jerzy-Roch NoferGerd Assmann
Mar 23, 2018·Pediatric Pulmonology·Nour Akil, Anthony J Fischer
Jan 7, 2018·Journal of Lipid Research·Michael C Phillips
Feb 17, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Robert S KissYves L Marcel
May 20, 2006·The Journal of Biological Chemistry·Doriane TrompierGiovanna Chimini
Dec 10, 2019·Bioscience, Biotechnology, and Biochemistry·Yusuke OkamotoKazumitsu Ueda
Jun 13, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Chieh Chang, Naoki Hisamoto
Jun 30, 2016·International Journal of Molecular Medicine·Sabrina FrixelMatthias Griese
Sep 9, 2017·European Journal of Ophthalmology·Nutsuchar WangtiraumnuayEsther Biswas-Fiss
Oct 8, 2016·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Jianhua ChenYongyong Shi
Feb 6, 2020·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Keiichiro Okuhira

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