Mechanisms of transthyretin amyloidogenesis. Antigenic mapping of transthyretin purified from plasma and amyloid fibrils and within in situ tissue localizations.
Mechanisms of transthyretin amyloidogenesis. Antigenic mapping of transthyretin purified from plasma and amyloid fibrils and within in situ tissue localizations.
复制标题
转甲状腺素蛋白淀粉样变性的机制。
DOI：
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发表时间：
1994
影响因子：
6
通讯作者：
P. Westermark
中科院分区：
文献类型：
--
作者：
Å. Gustavsson;Ulla Engstr;P. Westermark
甲状腺素运载蛋白 (TTR) 是老年系统性淀粉样变性和多种形式的家族性淀粉样变性中的主要淀粉样原纤维蛋白。然而，原纤维的内部组织实际上是未知的。目前尚不清楚原纤维内 TTR 分子的结构是否发生了实质性改变。在这项研究中，我们使用了各种抗原作图程序来确定正常 TTR、ATTR（淀粉样原纤维的 TTR）和原位淀粉样原纤维之间的主要抗原位点是否不同。使用标准免疫程序（即 ELISA、蛋白质印迹和免疫组织化学）、TTR 分子的合成肽、针对这些合成肽以及针对正常 TTR、ATTR 和碱降解淀粉样原纤维的抗血清来实现抗原图谱。我们的结果表明，正常血浆TTR上的抗原位点包括AB环和CD环。与这些环相关的氨基酸序列存在于 TTR 分子的外部。抗β-链H的抗血清仅与淀粉样原纤维中的TTR和ATTR发生反应，但不与正常血浆TTR或朗格汉斯岛中的TTR发生反应。我们的结果表明，与血浆 TTR 相比，淀粉样原纤维内的 TTR 构型发生了改变。
Transthyretin (TTR) is the major amyloid fibril protein in senile systemic amyloidosis and in several forms of familial amyloidoses. However, the internal organization of the fibrils is virtually unknown. It is not known whether the structure of the TTR molecules is substantially altered within the fibrils. In this study we used various antigenic mapping procedures to determine whether major antigenic sites differ between normal TTR, ATTR (TTR from amyloid fibrils), and in situ amyloid fibrils. Antigenic mapping was achieved using standard immunological procedures (ie, ELISA, Western blot, and immunohistochemistry), synthetic peptides of the TTR molecule, antisera against these synthetic peptides and against normal TTR, ATTR, and alkali-degraded amyloid fibrils. Our results show that the antigenic sites on normal plasma TTR include the AB loop and the CD loop. The amino acid sequences associated with these loops are present on the outside of the TTR molecule. Antiserum against beta-strand H reacted only with TTR in amyloid fibrils and ATTR but not with normal plasma TTR or TTR in the islets of Langerhans. Our results suggest that there is an altered configuration of TTR within amyloid fibrils when compared with plasma TTR.
识别阿尔茨海默病患者淀粉样蛋白病变的两种多克隆抗体的表位图。
DOI：
10.1042/bj2820517
发表时间：
1992
期刊：
The Biochemical journal
影响因子：
--
作者：
Ghiso,J;Wisniewski,T;Vidal,R;Rostagno,A;Frangione,B
通讯作者：
Frangione,B
影响因子：
15.9
作者：
SARAIVA, MJM;BIRKEN, S;GOODMAN, DS
通讯作者：
GOODMAN, DS