a Institute of Protein Biochemistry, Ulm University , Ulm , Germany.
b Core Unit Mass Spectrometry and Proteomics, Ulm University , Ulm , Germany.
Amyloid. 2019 Sep;26(3):164-170. doi: 10.1080/13506129.2019.1628015. Epub 2019 Jun 26.
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. 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. The fibrils show a consistent morphology in all four patients and exhibit an average width of ∼9.6 nm and an average pitch of ∼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. 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.
为了验证这样一个假说，即纤维形态和纤维蛋白一级结构在患有常见变异型系统性淀粉样变性 A 型（AA）淀粉样变的不同患者中是保守的。从 4 名患者的肾组织中提取了淀粉样纤维。用透射电子显微镜（TEM）对负染样本中的纤维形态进行了分析。通过质谱法确定了纤维蛋白的身份和片段长度。所有患者的纤维都呈现出一致的形态，平均宽度约为 9.6nm，平均螺距约为 112nm。所有纤维均由可分配给人血清淀粉样蛋白 A（SAA）1.1 蛋白的多肽链组成。所有片段均缺乏 N 端精氨酸残基，并在 C 端截断。在确切的 C 端切割位点方面存在差异。最突出的切割位点发生在残基 64-67 处。我们的数据表明，在分析的 4 名患者中，AA 淀粉样纤维在蛋白一级结构和纤维形态水平上是一致的。
