Inflammation protein SAA2.2 spontaneously forms marginally stable amyloid fibrils at physiological temperature.
Inflammation protein SAA2.2 spontaneously forms marginally stable amyloid fibrils at physiological temperature.
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炎症蛋白SAA2.2在生理温度下自发形成边缘稳定的淀粉样原纤维。
DOI：
10.1021/bi200856v
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发表时间：
2011
期刊：
影响因子：
2.9
通讯作者：
Colon,Wilfredo
中科院分区：
文献类型：
--
作者：
Ye,Zhuqiu;BayronPoueymiroy,Diane;Aguilera,JJavier;Srinivasan,Saipraveen;Wang,Yun;Serpell,LouiseC;Colon,Wilfredo
近四十年来，炎症相关蛋白血清淀粉样蛋白A（SAA）形成淀粉样纤维与淀粉样蛋白A（AA）淀粉样变性疾病在病理学上有联系。然而，在这里，我们发现非致病性小鼠SAA 2.2在37 °C下自发形成边缘稳定的淀粉样蛋白原纤维，其表现出交叉β结构，与硫磺素T结合，并通过成核依赖性接种机制形成原纤维。与大多数已知的淀粉样蛋白原纤维对热变性和化学变性的高稳定性相反，通过戊二醛交联/SDS-PAGE、硫磺素T荧光和光散射（OD 600）监测的实验表明，SAA 2.2的成熟淀粉样蛋白原纤维在>1.0 M尿素或>45 °C下孵育后解离。当考虑到SAA 2.2的非致病性性质及其在炎症反应期间血浆中浓度增加1000倍时，其在生理学样条件下的极端体外淀粉样蛋白原性表明SAA淀粉样蛋白可能在炎症期间发挥功能性作用。具有普遍意义的是，本文使用的方法的组合便于探索对尿素和温度敏感的淀粉样原纤维的稳定性。此外，我们的研究表明，类似于球状蛋白，它可以拥有从本质上无序的结构非常稳定，在vivomight中形成的淀粉样原纤维具有更广泛的稳定性比以前认识到的深刻的功能和病理意义。
For nearly four decades, the formation of amyloid fibrils by the inflammation-related protein serum amyloid A (SAA) has been pathologically linked to the disease amyloid A (AA) amyloidosis. However, here we show that the nonpathogenic murine SAA2.2 spontaneously forms marginally stable amyloid fibrils at 37 °C that exhibit cross-beta structure, binding to thioflavin T, and fibrillation by a nucleation-dependent seeding mechanism. In contrast to the high stability of most known amyloid fibrils to thermal and chemical denaturation, experiments monitored by glutaraldehyde cross-linking/SDS-PAGE, thioflavin T fluorescence, and light scattering (OD600) showed that the mature amyloid fibrils of SAA2.2 dissociate upon incubation in >1.0 M urea or >45 °C. When considering the nonpathogenic nature of SAA2.2 and its ∼1000-fold increased concentration in plasma during an inflammatory response, its extremein vitroamyloidogenicity under physiological-like conditions suggest that SAA amyloid might play a functional role during inflammation. Of general significance, the combination of methods used here is convenient for exploring the stability of amyloid fibrils that are sensitive to urea and temperature. Furthermore, our studies imply that analogous to globular proteins, which can possess structures ranging from intrinsically disordered to extremely stable, amyloid fibrils formedin vivomight have a broader range of stabilities than previously appreciated with profound functional and pathological implications.