Urea-induced denaturation of apolipoprotein serum amyloid A reveals marginal stability of hexamer.
Urea-induced denaturation of apolipoprotein serum amyloid A reveals marginal stability of hexamer.
复制标题
尿素诱导的载脂蛋白血清淀粉样蛋白 A 变性揭示了六聚体的边缘稳定性。
DOI：
10.1110/ps.051387005
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Colon,Wilfredo
中科院分区：
文献类型：
--
作者：
Wang,Limin;Colon,Wilfredo
血清淀粉样蛋白A(SAA)是一种急性时相反应性蛋白，主要与血浆中的高密度脂蛋白结合。炎症时，血浆SAA浓度可显著增加，有时会导致淀粉样蛋白A(AA)淀粉样变性的发展，这涉及到主要器官中SAA淀粉样纤维的沉积。我们先前发现小鼠的SAA2.2异构体以六聚体的形式存在于水溶液中，其中包含一个中心通道。在这里，我们利用各种生物物理和生化技术证明，SAA2.2六聚体可以被∼2M尿素完全解离成单体，但其α-螺旋结构却发生了协同丢失。然而，有限的胰酶在尿素中的蛋白分解实验显示了一个保守的消化图谱，这表明在尿素变性状态下SAA2.2的主要骨架拓扑特征被保留。六聚体SAA2.2的边缘稳定性和变性单体蛋白中残基结构的存在表明，这两种形式在体内可能相互转换，发挥不同的功能，以满足正常生理条件下和炎症刺激下的不同需要。
Serum Amyloid A (SAA) is an acute phase reactant protein that is predominantly found bound to high‐density lipoprotein in plasma. Upon inflammation, the plasma concentration of SAA can increase dramatically, occasionally leading to the development of amyloid A (AA) amyloidosis, which involves the deposition of SAA amyloid fibrils in major organs. We previously found that the murine isoform SAA2.2 exists in aqueous solution as a hexamer containing a central channel. Here we show using various biophysical and biochemical techniques that the SAA2.2 hexamer can be totally dissociated into monomer by ∼2 M urea, with the concerted loss of its α‐helical structure. However, limited trypsin proteolysis experiments in urea showed a conserved digestion profile, suggesting the preservation of major backbone topological features in the urea‐denatured state of SAA2.2. The marginal stability of hexameric SAA2.2 and the presence of residual structure in the denatured monomeric protein suggest that both forms may interconvert in vivo to exert different functions to meet the various needs during normal physiological conditions and in response to inflammatory stimuli.