Morphological and primary structural consistency of fibrils from different AA patients (common variant)
Morphological and primary structural consistency of fibrils from different AA patients (common variant)
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DOI：
10.1080/13506129.2019.1628015
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发表时间：
2019-06-24
影响因子：
5.5
通讯作者：
Fandrich, Marcus
中科院分区：
文献类型：
--
作者：
Liberta, Falk;Rennegarbe, Matthies;Fandrich, Marcus
目的：为了检验原纤维形态和原纤维蛋白一级结构在患有系统性淀粉样蛋白A（AA）淀粉样变性的常见变体的不同患者中是保守的这一假设。方法：从4例患者的肾组织中提取淀粉样纤维。用透射电子显微镜（TEM）在负染色样品中分析原纤维形态。原纤维蛋白的身份和片段长度通过使用质谱法测定。结果如下：在所有四名患者中，原纤维显示出一致的形态，并表现出类似于9.6 nm的平均宽度和类似于112 nm的平均节距。所有原纤维都由多肽链组成，这些多肽链可归属于人血清淀粉样蛋白A（SAA）1.1蛋白。所有片段均缺少N-末端精氨酸残基，并且C-末端被截短。关于确切的C-末端切割位点存在差异。最突出的切割位点发生在残基64-67处。结论：我们的数据表明，AA淀粉样纤维是一致的蛋白质一级结构和纤维形态的水平在四个分析的患者。
Aims: To test the hypothesis that the fibril morphology and the fibril protein primary structure are conserved across different patients suffering from the common variant of systemic Amyloid A (AA) amyloidosis. Methods: Amyloid fibrils were extracted from the renal tissue of four patients. The fibril morphology was analysed in negatively stained samples with transmission electron microscopy (TEM). The fibril protein identity and fragment length were determined by using mass spectrometry. Results: The fibrils show a consistent morphology in all four patients and exhibit an average width of similar to 9.6 nm and an average pitch of similar to 112 nm. All fibrils are composed of polypeptide chains that can be assigned to human serum amyloid A (SAA) 1.1 protein. All fragments lack the N-terminal arginine residue and are C-terminally truncated. Differences exist concerning the exact C-terminal cleavage site. The most prominent cleavage site occurs at residues 64-67. Conclusions: Our data demonstrate that AA amyloid fibrils are consistent at the level of the protein primary structure and fibril morphology in the four analysed patients.