Two motifs within the tau microtubule-binding domain mediate its association with the hsc70 molecular chaperone.
Two motifs within the tau microtubule-binding domain mediate its association with the hsc70 molecular chaperone.
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DOI：
10.1002/jnr.21721
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发表时间：
2008-09
影响因子：
4.2
通讯作者：
Lee, Gloria
中科院分区：
文献类型：
--
作者：
Sarkar, Mitul;Kuret, Jeff;Lee, Gloria
Tau是一种具有多个磷酸化位点的微管相关蛋白，形成与阿尔茨海默病和其他几种神经退行性疾病（称为Tau病）中的神经退行性疾病相关的聚集体。Hsc 70是一种高表达的组成型分子伴侣，可以驱动蛋白质的构象变化，防止其底物的聚集，识别错误折叠的底物，并促进其降解。在这里，我们发现hsc 70在体外和体内结合到tau蛋白的微管结合域，而不需要tau蛋白磷酸化。结合需要hsc 70的羧基末端区域，包括其肽结合和可变结构域。我们已经确定了两个hsc 70结合位点的tau蛋白和疏水氨基酸的hsc 70结合至关重要。有趣的是，这些hsc 70结合位点对应于先前报道的促进tau聚集的β结构元件。因此，hsc 70结合可能直接抑制tau寡聚化和聚集之前的tau-tau相互作用。我们的结果为研究hsc 70-tau相互作用如何影响正常细胞和疾病中tau的命运提供了重要的刺激。
Tau, a microtubule-associated protein with multiple phosphorylation sites, forms aggregates that correlate with neurodegeneration in Alzheimer Disease and several other neurodegenerative diseases, termed tauopathies. Hsc70 is a highly-expressed constitutive chaperone that can drive conformational change in proteins, prevent the aggregation of its substrates, recognize misfolded substrates, and facilitate their degradation. Here, we show that hsc70 binds to the microtubule-binding domain of tau in vitro and in vivo, without an absolute requirement for tau phosphorylation. Binding requires a carboxy-terminal region of hsc70 comprising its peptide-binding and variable domains. We have identified two hsc70-binding sites on tau and hydrophobic amino acids crucial for hsc70-binding. Interestingly, these hsc70-binding sites correspond to the β-structure elements that have been previously reported to facilitate tau aggregation. Thus, it is possible that hsc70 binding might directly inhibit tau-tau interactions that precede tau oligomerization and aggregation. Our results provide an important stimulus for research into how the hsc70-tau interaction might affect tau fate in normal cells and in disease.
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DOI：
10.1083/jcb.115.3.717
发表时间：
1991-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Butner KA;Kirschner MW
通讯作者：
Kirschner MW
影响因子：
56.9
作者：
CHIANG, HL;TERLECKY, SR;DICE, JF
通讯作者：
DICE, JF
影响因子：
56.9
作者：
BECKMANN, RP;MIZZEN, LA;WELCH, WJ
通讯作者：
WELCH, WJ
影响因子：
4.8
作者：
Goode, BL;Chau, M;Feinstein, SC
通讯作者：
Feinstein, SC
在发育调节的tau的重复区域中，新型微管结合和组装结构域的鉴定。
影响因子：
7.8
作者：
Goode, B L;Feinstein, S C
通讯作者：
Feinstein, S C