Influence of tertiary structure domain properties on the functionality of apolipoprotein A-I

Biochemistry
Masafumi TanakaMichael C Phillips

Abstract

The tertiary structure of apolipoprotein (apo) A-I and the contributions of structural domains to the properties of the protein molecule are not well defined. We used a series of engineered human and mouse apoA-I molecules in a range of physical-biochemical measurements to address this issue. Circular dichroism measurements of alpha-helix thermal unfolding and fluorescence spectroscopy measurements of 8-anilino-1-napthalenesulfonic acid binding indicate that removal of the C-terminal 54 amino acid residues from human and mouse apoA-I has similar effects; the molecules are only slightly destabilized, and there is a decrease in hydrophobic surface exposure. These results are consistent with both human and mouse apoA-I adopting a two-domain tertiary structure, comprising an N-terminal antiparallel helix bundle domain and a separate less ordered C-terminal domain. Mouse apoA-I is significantly less resistant than human apoA-I to thermal and chemical denaturation; the midpoint of thermal unfolding of mouse apoA-I at 45 degrees C is 15 degrees C lower and the midpoint of guanidine hydrochloride denaturation (D1/2) occurs at 0.5 M as compared to 1.0 M for human apoA-I. These differences reflect the overall greater stability of the hel...Continue Reading

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Citations

Oct 31, 2013·Journal of Medicinal Chemistry·Luke J LemanM Reza Ghadiri
Aug 4, 2010·The Journal of Biological Chemistry·Charulatha VedhachalamMichael C Phillips
Aug 27, 2010·The Journal of Biological Chemistry·Iliya LefterovRadosveta Koldamova
Nov 13, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Eric T AlexanderMichael C Phillips
Sep 30, 2009·Journal of Lipid Research·Sissel Lund-KatzMichael C Phillips
Mar 9, 2013·Journal of Lipid Research·Jonathan Dalla-RivaJens O Lagerstedt
Jun 3, 2008·Journal of Lipid Research·Michael J ThomasMary G Sorci-Thomas
Feb 13, 2014·PloS One·Timothy J Sontag, Catherine A Reardon
Dec 25, 2015·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Hiroyuki NakajimaNaomi Sakashita
Jan 20, 2016·Journal of Peptide Science : an Official Publication of the European Peptide Society·Hirokazu KariyazonoHiroyuki Saito
Aug 16, 2011·Biochimica Et Biophysica Acta·Nicholas N LyssenkoMichael C Phillips
Nov 3, 2010·Biochimica Et Biophysica Acta·Masafumi TanakaHiroyuki Saito
Dec 3, 2008·Journal of Peptide Science : an Official Publication of the European Peptide Society·Masafumi TanakaHiroyuki Saito
May 24, 2011·Biochimica Et Biophysica Acta·Alexander D Dergunov
May 18, 2016·Laboratory Investigation; a Journal of Technical Methods and Pathology·Dimitry A ChistiakovYuri V Bobryshev
Sep 27, 2019·Pharmacological Reviews·Dongdong WangAtanas G Atanasov
Mar 22, 2013·Molecular and Cellular Biochemistry·Alexander D Dergunov
Apr 25, 2015·Biochemistry·Therese SchulthessJoachim Seelig
Feb 22, 2013·Biochemistry·David NguyenMichael C Phillips

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