Post-translational modification of amyloid a protein in patients with AA amyloidosis.
Post-translational modification of amyloid a protein in patients with AA amyloidosis.
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AA 型淀粉样变性患者中淀粉样蛋白 a 的翻译后修饰。
DOI：
10.1080/13506129.2021.1997985
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Benson,MerrillD
中科院分区：
文献类型：
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作者：
Kluve-Beckerman,Barbara;Smith,JustinT;Ivancic,Carlie;Benson,MerrillD
AA淀粉样变性是由淀粉样蛋白A（AA）蛋白（血清淀粉样蛋白A（SAA）的氨基（N）末端片段）组成的不溶性β-折叠片原纤维的细胞外沉积引起的疾病。这些沉积物破坏了组织结构，损害了器官功能。虽然该病是全身性的，但肾小球沉积是最常见的表现。AA淀粉样变性的主要原因是持续或复发性炎症伴随SAA水平升高。决定SAA转化为AA淀粉样纤维的因素尚未完全解决。在此，我们提出了液相色谱串联质谱（LC-MS/MS）分析AA蛋白纯化从八例AA淀粉样变性。第一次，翻译后修饰（PTM），包括氨甲酰化，乙酰化和氧化，被确定在AA肽;所有八个样品显示一定程度的PTM。6个样品中的淀粉样蛋白包含来自SAA 1的肽，很少或没有来自SAA 2的肽，而另外两个样品含有SAA 1和SAA 2衍生的肽。以Arg 1开始的N-末端AA肽以及以Ser 2开始的AA肽存在于八个样品中的五个中，而其他三个样品中的所有或几乎所有的N-末端肽缺乏Arg 1。这些数据表明，多种AA淀粉样蛋白可以包括淀粉样纤维中的亚基，并提高PTM可能在纤维形成中发挥作用的可能性。
AA amyloidosis is a disease caused by extracellular deposition of insoluble β-pleated sheet fibrils composed of amyloid A (AA) protein, an amino (N)-terminal fragment of serum amyloid A (SAA). The deposits disrupt tissue structure and compromise organ function. Although the disease is systemic, deposition in kidney glomeruli is the most common manifestation. The leading cause of AA amyloidosis is sustained or recurrent inflammation accompanied by elevated levels of SAA. Factors determining the conversion of SAA to AA amyloid fibrils have yet to be fully resolved. Herein, we present liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis of AA proteins purified from eight patients with AA amyloidosis. For the first time, post-translational modifications (PTM), including carbamylation, acetylation and oxidation, were identified on AA peptides; all eight samples showed some degree of PTM. The amyloid in 6 samples comprised peptides derived from SAA1 with few or none from SAA2, while the other two samples contained both SAA1- and SAA2-derived peptides. N-terminal AA peptides beginning with Arg1 as well as AA peptides starting with Ser2 were present in five of the eight samples, while all or nearly all of the N-terminal peptides in the other three samples lacked Arg1. These data demonstrate that multiple species of AA amyloid proteins can comprise the subunits in amyloid fibrils and raise the possibility that PTM may play a role in fibrillogenesis.