Polymorphisms of mouse apolipoprotein A-II alter its physical and functional nature.
Polymorphisms of mouse apolipoprotein A-II alter its physical and functional nature.
复制标题
DOI：
10.1371/journal.pone.0088705
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Reardon CA
中科院分区：
文献类型：
--
作者：
Sontag TJ;Reardon CA
ApoA-II是HDL上第二丰富的蛋白质，占总蛋白质的约20%，但其功能仍然仅被部分表征。最近的方法学改进允许重组表达和表征的人apoA-II的股份只有55%的序列同源性与鼠apoA-II。在这里，我们描述了纯化的两个最常见的多态性变体apoA-II中发现的近交系小鼠品系，不同的3个氨基酸位点。具有变体apoA-IIa的C57 BL/6小鼠的血浆HDL水平低于具有变体apoA-IIb的FVB/N小鼠。这两种变体的螺旋结构的表征揭示了FVB/N apoA-II的更多α-螺旋结构。这些变化不改变两种apoA-II变体的脂质或HDL结合，但显著增加FVB/N变体促进ABCA 1和ABCG 1介导的细胞胆固醇流出的能力。这些差异可能是差异改变血浆HDL apoA-II水平。在体内，C57和FVB apoA-II蛋白水平均不受apoE缺乏的影响，而apoE/apoA-I双重缺乏导致血浆FVB apoA-II降低50%，但导致血浆中C57 apoA-II水平不可检测。FVB apoA-II能够在不存在apoE或apoA-I的情况下形成HDL颗粒。
ApoA-II is the second most abundant protein on HDL making up ∼20% of the total protein but its functions have still only been partially characterized. Recent methodological improvements have allowed for the recombinant expression and characterization of human apoA-II which shares only 55% sequence homology with murine apoA-II. Here we describe the purification of the two most common polymorphic variants of apoA-II found in inbred mouse strains, differing at 3 amino acid sites. C57BL/6 mice having variant apoA-IIa have lower plasma HDL levels than FVB/N mice that have variant apoA-IIb. Characterization of the helical structure of these two variants reveals a more alpha-helical structure for the FVB/N apoA-II. These changes do not alter the lipid or HDL binding of the two apoA-II variants, but significantly increase the ability of the FVB/N variant to promote both ABCA1 and ABCG1 mediated cellular cholesterol efflux. These differences may be differentially altering plasma HDL apoA-II levels. In vivo, neither C57 nor FVB apoA-II protein levels are affected by the absence of apoE, while an apoE/apoA-I double deficiency results in a 50% decrease of plasma FVB apoA-II but results in undetectable levels of C57 apoA-II in the plasma. FVB apoA-II is able to form an HDL particle in the absence of apoE or apoA-I.
登录
查看更多内容
影响因子：
6.5
作者：
Sankaranarayanan, Sandhya;Oram, John F.;Asztalos, Bela F.;Vaughan, Ashley M.;Lund-Katz, Sissel;Adorni, Maria Pia;Phillips, Michael C.;Rothblat, George H.
通讯作者：
Rothblat, George H.
影响因子：
5.3
作者：
OSADA, J;FERNANDEZSANCHEZ, A;PALACIOSALAIZ, E
通讯作者：
PALACIOSALAIZ, E
DOI：
10.1016/j.bbalip.2009.09.012
发表时间：
2010-01-01
影响因子：
4.8
作者：
Smith, Loren E.;Davidson, W. Sean
通讯作者：
Davidson, W. Sean
影响因子：
20.1
作者：
Moore, RE;Navab, M;Rader, DJ
通讯作者：
Rader, DJ
影响因子：
4.8
作者：
Oram, JF;Vaughan, AM;Stocker, R
通讯作者：
Stocker, R