Jakes R, Novak M, Davison M, Wischik C M
MRC Laboratory of Molecular Biology, Cambridge.
EMBO J. 1991 Oct;10(10):2725-9. doi: 10.1002/j.1460-2075.1991.tb07820.x.
The microtubule associated protein tau is incorporated into the pronase resistant core of the paired helical filament (PHF) in such a way that the repeat region is protected from proteases, but can be released as a major 12 kDa species from the PHF core by formic acid treatment and by boiling in SDS. This fragment retains the ability to aggregate in the presence of SDS. Detailed sequence analysis of the 12 kDa species shows that it consists of a mixture of peptides derived from the repeat region of 3- and 4-repeat tau isoforms comigrating as a single electrophoretic band. However, the 4-repeat isoforms released from the core lack either the first or the last repeat. The pronase-protected region of tau within the PHF core is therefore restricted to three repeats, regardless of isoform. The alignment of cleavage sites at homologous positions within tandem repeats after protease treatment indicates that the tau-core association is precisely constrained by the tandem repeat structure of the tau molecule.
微管相关蛋白tau以这样一种方式整合到双螺旋丝（PHF）的抗链霉蛋白酶核心中，即重复区域受到蛋白酶的保护，但通过甲酸处理和在SDS中煮沸，可以从PHF核心中作为主要的12 kDa物质释放出来。该片段在SDS存在下仍保留聚集能力。对12 kDa物质的详细序列分析表明，它由来自3重复和4重复tau异构体重复区域的肽混合物组成，这些肽作为单个电泳条带一起迁移。然而，从核心释放的4重复异构体要么缺少第一个重复，要么缺少最后一个重复。因此，无论异构体如何，PHF核心内tau的抗链霉蛋白酶保护区域都限于三个重复。蛋白酶处理后串联重复内同源位置的切割位点比对表明，tau与核心的结合受到tau分子串联重复结构的精确限制。
