Weinberg R B, Anderson R A, Cook V R, Emmanuel F, Denefle P, Hermann M, Steinmetz A
Section of Gastroenterology, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
J Lipid Res. 2000 Sep;41(9):1410-8.
To gain insight into the evolution and function of apolipoprotein A-IV (apoA-IV) we compared structural and interfacial properties of chicken apoA-IV, human apoA-IV, and a recombinant human apoA-IV truncation mutant lacking the carboxyl terminus. Circular dichroism thermal denaturation studies revealed that the thermodynamic stability of the alpha-helical structure in chicken apoA-IV (DeltaH = 71.0 kcal/mol) was greater than that of human apoA-IV (63.6 kcal/mol), but similar to that of human apoA-I (73.1 kcal/mol). Fluorescence chemical denaturation studies revealed a multiphasic red shift with a 65% increase in relative quantum yield that preceded loss of alpha-helical structure, a phenomenon previously noted for human apoA-IV. The elastic modulus of chicken apoA-IV at the air/water interface was 13.7 mN/m, versus 21.7 mN/m for human apoA-IV and 7.6 mN/m for apoA-I. The interfacial exclusion pressure of chicken apoA-IV for phospholipid monolayers was 31.1 mN/m, versus 33.0 mN/m for human A-I and 28.5 mN/m for apoA-IV. We conclude that the secondary structural features of chicken apoA-IV more closely resemble those of human apoA-I, which may reflect the evolution of apoA-IV by intraexonic duplication of the apoA-I gene. However, the interfacial properties of chicken apoA-IV are intermediate between those of human apoA-I and apoA-IV, which suggests that chicken apoA-IV may represent an ancestral prototype of mammalian apoA-IV, which subsequently underwent further structural change as an evolutionary response to the requisites of mammalian lipoprotein metabolism.
为深入了解载脂蛋白A-IV（apoA-IV）的进化及功能，我们比较了鸡apoA-IV、人apoA-IV以及一种缺失羧基末端的重组人apoA-IV截短突变体的结构和界面特性。圆二色性热变性研究表明，鸡apoA-IV中α-螺旋结构的热力学稳定性（ΔH = 71.0千卡/摩尔）高于人apoA-IV（63.6千卡/摩尔），但与人apoA-I（73.1千卡/摩尔）相似。荧光化学变性研究显示，在α-螺旋结构丧失之前，会出现多相红移，相对量子产率增加65%，这一现象此前在人apoA-IV中也有发现。鸡apoA-IV在空气/水界面的弹性模量为13.7毫牛/米，人apoA-IV为21.7毫牛/米，apoA-I为7.6毫牛/米。鸡apoA-IV对磷脂单层的界面排斥压力为31.1毫牛/米，人apoA-I为33.0毫牛/米，apoA-IV为28.5毫牛/米。我们得出结论，鸡apoA-IV的二级结构特征与人apoA-I更为相似，这可能反映了apoA-IV是通过apoA-I基因的外显子内复制进化而来。然而，鸡apoA-IV的界面特性介于人apoA-I和apoA-IV之间，这表明鸡apoA-IV可能代表了哺乳动物apoA-IV的祖先原型，随后它作为对哺乳动物脂蛋白代谢需求的一种进化反应经历了进一步的结构变化。
