Conformational analysis of apolipoprotein E3/E4 heteromerization

The FEBS Journal
Kai-Han TuVasanthy Narayanaswami

Abstract

Apolipoprotein E (apoE) is a 299 residue, exchangeable apolipoprotein that has essential roles in cholesterol homeostasis and reverse cholesterol transport. It is a two-domain protein with the C-terminal (CT) domain mediating protein self-association via helix-helix interactions. In humans, the APOE gene is polymorphic with three common alleles, ε2, ε3, and ε4, occurring in frequencies of ~ 5%, 77%, and 18%, respectively. Heterozygotes expressing apoE3 and apoE4 isoforms, which differ in residue at position 112 in the N-terminal domain (C112 in apoE3 and R112 in apoE4), represent the highest population of ε4 carriers, an allele highly associated with Alzheimer's disease. The objective of this study was to determine if apoE3 and apoE4 have the ability to hybridize to form a heteromer in lipid-free state. Refolding an equimolar mixture of His-apoE3 and FLAG-apoE4 (or vice versa) followed by pull-down and immunoblotting indicated formation of apoE3/apoE4 heteromers. Förster resonance energy transfer between donor fluorophore on one isoform and acceptor on the other, both located in the respective CT domains, revealed a distance of separation of ~ 46 Å between the donor/acceptor pair. Similarly, a quencher placed on one was able to...Continue Reading

References

Jan 1, 1988·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·J DavignonC F Sing
Sep 1, 1986·The Journal of Clinical Investigation·R E GreggH B Brewer
Jan 1, 1994·Advances in Protein Chemistry·K H Weisgraber
Mar 10, 1999·The American Journal of Physiology·C D MamotteR R Taylor
Dec 22, 1999·Neurobiology of Aging·C E Finch, R M Sapolsky
Jan 25, 2000·The Journal of Biological Chemistry·J A MorrowK H Weisgraber
Sep 6, 2000·The Journal of Biological Chemistry·M A PeruginiG J Howlett
Sep 27, 2000·Journal of Neuropathology and Experimental Neurology·A M Saunders
Jun 28, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A Von EckardsteinG Assmann
Nov 10, 2001·Annual Review of Genomics and Human Genetics·R W Mahley, S C Rall
Feb 21, 2002·Trends in Endocrinology and Metabolism : TEM·Dudley K StricklandW Scott Argraves
Nov 19, 2003·Journal of Molecular Biology·Nicole ChoyVasanthy Narayanaswami
Jan 24, 2004·The Journal of Biological Chemistry·Vasanthy NarayanaswamiW Sean Davidson
Apr 23, 2004·The Quarterly Review of Biology·Caleb E Finch, Craig B Stanford
May 5, 2006·PLoS Medicine·Simon P MooijaartRudi G J Westendorp
Aug 25, 2007·Biochemistry·Yonghong ZhangJianjun Wang
Dec 25, 2008·Journal of Lipid Research·Robert W MahleyYadong Huang
Aug 4, 2009·Future Lipidology·Elena Posse de Chaves, Vasanthy Narayanaswami
Nov 4, 2010·Journal of Geriatric Psychiatry and Neurology·Lynn M BekrisDebby W Tsuang
Feb 26, 2011·Lancet Neurology·Philip B VergheseDavid M Holtzman
Aug 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jianglei ChenJianjun Wang
Oct 27, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tadafumi HashimotoBradley T Hyman
Oct 30, 2012·Archives of Biochemistry and Biophysics·Tuyen N TranVasanthy Narayanaswami
May 29, 2014·Biochemical and Biophysical Research Communications·Sea H KimVasanthy Narayanaswami
Jul 31, 2014·The Journal of Biological Chemistry·Michael C Phillips
Oct 21, 2014·IUBMB Life·Michael C Phillips
Jun 10, 2016·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Robert W Mahley

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