The β-slip:: A novel concept in transthyretin amyloidosis
The β-slip:: A novel concept in transthyretin amyloidosis
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DOI：
10.1016/s1097-2765(00)00117-9
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发表时间：
2000-11-01
期刊：
影响因子：
16
通讯作者：
Sauer-Eriksson, AE
中科院分区：
文献类型：
--
作者：
Eneqvist, T;Andersson, K;Sauer-Eriksson, AE
甲状腺素运载蛋白是与两种形式的淀粉样疾病相关的四聚体血浆蛋白。以2.3埃分辨率测定的高度淀粉样蛋白生成的甲状腺素运载蛋白三重突变体TTRG53 S/E54 D/L55 S的结构揭示了一种新的构象：β-滑动。β链D中的三个残基位移将Leu-58置于通常由Leu-55占据的位置，现在突变为丝氨酸。β-滑移最好在四个单体中的两个中定义，其中它使新的蛋白质-蛋白质相互作用到达通常涉及与视黄醇结合蛋白形成复合物的区域。这种相互作用产生了独特的包装安排，其中两个蛋白质螺旋联合收割机结合，形成一个双螺旋与纤维衍射和电子显微镜数据一致。基于这些发现，提出了一种新的甲状腺素运载蛋白淀粉样蛋白形成模型。
Transthyretin is a tetrameric plasma protein associated with two forms of amyloid disease. The structure of the highly amyloidogenic transthyretin triple mutant TTRG53S/E54D/L55S determined at 2.3 Angstrom resolution reveals a novel conformation: the beta -slip. A three-residue shift in beta strand D places Leu-58 at the position normally occupied by Leu-55 now mutated to serine. The beta -slip is best defined in two of the four monomers, where it makes new protein-protein interactions to an area normally involved in complex formation with retinol-binding protein. This interaction creates unique packing arrangements, where two protein helices combine to form a double helix in agreement with fiber diffraction and electron microscopy data. Based on these findings, a novel model for transthyretin amyloid formation is presented.