Serum amyloid A 2.2 refolds into a octameric oligomer that slowly converts to a more stable hexamer.
Serum amyloid A 2.2 refolds into a octameric oligomer that slowly converts to a more stable hexamer.
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血清淀粉样蛋白 A 2.2 重新折叠成八聚寡聚体，然后缓慢转化为更稳定的六聚体。
DOI：
10.1016/j.bbrc.2011.03.090
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发表时间：
2011
影响因子：
3.1
通讯作者：
Colon,Wilfredo
中科院分区：
文献类型：
--
作者：
Wang,Yun;Srinivasan,Saipraveen;Ye,Zhuqiu;JavierAguilera,J;Lopez,MariaM;Colon,Wilfredo
血清淀粉样蛋白A(SAA)是一种炎性蛋白，主要与血浆中的高密度脂蛋白结合，具有多种生物学和病理作用。我们先前发现，小鼠SAA2.2异构体在4-20℃时以边缘稳定的六聚体存在于水溶液中，但在37℃时成为一种固有的无序蛋白质。这里我们展示了当尿素变性的SAA2.2被透析到缓冲液中(pH 8.0，4℃)时，它主要折叠成八聚体。根据SAA2.2的浓度，八聚体在4℃孵育数天到数周后转变为六聚体结构。用圆二色谱监测八聚体和六聚体的热变性表明，八聚体∼10℃不稳定，变性中点为∼22℃。因此，SAA2.2通过折叠成不太稳定但更容易获得的八聚体物种而被动力学捕获。SAA2.2在体外形成不同低聚体物种的能力及其边缘稳定性表明，SAA的结构可能在体内被调节以形成不同的生物相关物种。
Serum amyloid A (SAA) is an inflammatory protein predominantly bound to high-density lipoprotein in plasma and presumed to play various biological and pathological roles. We previously found that the murine isoform SAA2.2 exists in aqueous solution as a marginally stable hexamer at 4–20 °C, but becomes an intrinsically disordered protein at 37 °C. Here we show that when urea-denatured SAA2.2 is dialyzed into buffer (pH 8.0, 4 °C), it refolds mostly into an octameric species. The octamer transitions to the hexameric structure upon incubation from days to weeks at 4 °C, depending on the SAA2.2 concentration. Thermal denaturation of the octamer and hexamer monitored by circular dichroism showed that the octamer is ∼10 °C less stable, with a denaturation mid point of ∼22 °C. Thus, SAA2.2 becomes kinetically trapped by refolding into a less stable, but more kinetically accessible octameric species. The ability of SAA2.2 to form different oligomeric speciesin vitroalong with its marginal stability, suggest that the structure of SAA might be modulatedin vivoto form different biologically relevant species.