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单克隆抗体MN423的Fab片段的制备、结晶及初步X射线分析,揭示阿尔茨海默病成对螺旋丝的结构特征。

Preparation, crystallization and preliminary X-ray analysis of the Fab fragment of monoclonal antibody MN423, revealing the structural aspects of Alzheimer's paired helical filaments.

作者信息

Csóková Natália, Skrabana Rostislav, Urbániková L'ubica, Kovácech Branislav, Popov Alexander, Sevcík Jozef, Novák Michal

机构信息

Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, 845 10 Bratislava, Slovakia.

出版信息

Protein Pept Lett. 2006;13(9):941-4. doi: 10.2174/092986606778256180.

Abstract

Monoclonal antibody (mAb) MN423 recognizes Alzheimer's disease specific conformation of tau protein assembled into paired helical filaments (PHF). Since the three-dimensional structure of PHF is currently unavailable, the structure of MN423 binding site could provide important information about PHF conformation with the consequences for the Alzheimer's disease prevention and cure. Fab fragment of MN423 was prepared and purified. We have identified two different conditions for crystallization of the Fab fragment that yielded two crystal forms. They diffracted to 3.0 and 1.6 A resolution with four and one molecule in the asymmetric unit, respectively. Both crystal forms belonged to the space group P2(1) with unit cell parameters a = 76.4 A, b = 138.4 A, c = 92.4 A, beta = 101.9 degrees , and a = 71.5 A, b = 36.8 A, c = 85.5 A, beta = 113.9 degrees .

摘要

单克隆抗体(mAb)MN423可识别组装成双螺旋丝(PHF)的tau蛋白的阿尔茨海默病特异性构象。由于目前尚无法获得PHF的三维结构,MN423结合位点的结构可为PHF构象提供重要信息,这对阿尔茨海默病的预防和治疗具有重要意义。制备并纯化了MN423的Fab片段。我们确定了两种不同的条件用于Fab片段的结晶,得到了两种晶体形式。它们分别以3.0 Å和1.6 Å的分辨率衍射,非对称单元中分别有四个和一个分子。两种晶体形式均属于空间群P2(1),晶胞参数分别为a = 76.4 Å,b = 138.4 Å,c = 92.4 Å,β = 101.9°,以及a = 71.5 Å,b = 36.8 Å,c = 85.5 Å,β = 113.9°。

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