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首页> 外文期刊>Biochemistry >Effect of Zinc, Copper, and Calcium on the Structure and Stability of Serum Amyloid A
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Effect of Zinc, Copper, and Calcium on the Structure and Stability of Serum Amyloid A

机译：锌，铜和钙对血清淀粉样蛋白A结构和稳定性的影响

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Serum amyloid A (SAA) is a highly conserved acute phase reactant protein, and its concentration in serum can increase up to ~1000 times after an inflammatory stimuli. SAA is mainly associated with high-density lipoproteins in serum, and its main function appears to involve cholesterol transport and lipid metabolism. However, SAA has also been associated with many other functions and a number of diseases, although these potential links remain poorly understood. The three-dimensional structure of SAA is not known, but we have shown that murine SAA2.2 can exist in solution as a marginally stable hexamer, which at 37 °C dissociates to a monomeric species that misfolds irreversibly and self-assembles into amyloid fibrils. Thus, the structure and function of SAA in vivo appear to be modulated when it binds to other proteins or small ligands. Herein, the effect of copper (Cu~(2+)), zinc (Zn~(2+)), and calcium (Ca~(2+)) on the structure and stability of SAA2.2 in aqueous solution was examined using various probes of quaternary, tertiary, and secondary structure. At different concentrations of metals, including those found in the serum, the results show that the structure and stability of SAA2.2 are differently affected depending on the metal type and concentration. Copper (10-100mu M) was found to shift the equilibrium from hexamer to monomer without affecting significantly the stability of the tertiary and secondary structure of SAA2.2. In contrast, zinc (1 -10mu M) bound to SAA2.2 and stabilized its quaternary, tertiary, and secondary structure. Calcium (1 - 10 mM) destabilized all elements of SAA2.2 structure and induced its aggregation at 10 mM. Complete aggregation of SAA2.2 was also observed when it was incubated with 1 mM Cu~(2+) or Zn~(2+), further demonstrating the tenuous structure and stability of SAA2.2. Thus, these results suggest that the many functional and pathological roles attributed to SAA may rely on its precarious structure, modulated by its interaction with ligands under homeostasis conditions and during the acute phase response.
机译：血清淀粉样蛋白A（SAA）是一种高度保守的急性期反应蛋白，在炎症刺激后其血清中的浓度可增加约1000倍。 SAA主要与血清中的高密度脂蛋白有关，其主要功能似乎涉及胆固醇转运和脂质代谢。然而，尽管这些潜在的联系仍知之甚少，但SAA还与许多其他功能和许多疾病相关联。 SAA的三维结构尚不清楚，但我们已经证明鼠类SAA2.2可以以边际稳定的六聚体形式存在于溶液中，该六聚体在37°C时解离为不可逆折叠并自组装成淀粉样原纤维的单体物种。 。因此，当SAA与其他蛋白质或小的配体结合时，其体内的结构和功能似乎受到调节。在本文中，使用以下方法研究了铜（Cu〜（2+）），锌（Zn〜（2+））和钙（Ca〜（2+））对SAA2.2水溶液结构和稳定性的影响。四级，三级和二级结构的各种探针。结果表明，在不同浓度的金属（包括血清中发现的金属）下，SAA2.2的结构和稳定性会根据金属类型和浓度而受到不同的影响。发现铜（10-100μM）使平衡从六聚体转变为单体，而没有显着影响SAA2.2的三级和二级结构的稳定性。相反，锌（1-10μM）与SAA2.2结合并稳定了其四级，三级和二级结构。钙（1-10 mM）使SAA2.2结构的所有元素不稳定，并在10 mM时诱导其聚集。当将SAA2.2与1 mM Cu〜（2+）或Zn〜（2+）一起孵育时，也观察到SAA2.2的完全聚集，进一步证明了SAA2.2的脆弱结构和稳定性。因此，这些结果表明，归因于SAA的许多功能和病理作用可能取决于其不稳定的结构，该结构受其在稳态条件下和急性期反应期间与配体的相互作用所调节。

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