Hsp70 oligomerization is mediated by an interaction between the interdomain linker and the substrate-binding domain.
Hsp70 oligomerization is mediated by an interaction between the interdomain linker and the substrate-binding domain.
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DOI：
10.1371/journal.pone.0067961
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Cremades N
中科院分区：
文献类型：
--
作者：
Aprile FA;Dhulesia A;Stengel F;Roodveldt C;Benesch JL;Tortora P;Robinson CV;Salvatella X;Dobson CM;Cremades N
热休克蛋白（Hsp）70家族的寡聚化在体外和体内都有大量文献记载，尽管这一过程的机制、所涉及的特定蛋白质区域的身份以及生理相关性仍不清楚。我们通过纳升电喷雾电离质谱、光谱学和定量尺寸排阻色谱法研究了一系列人Hsp70变体的寡聚特性。我们的结果表明，Hsp70寡聚化是通过一个分子的结构域间连接体与另一个分子的底物结合结构域之间的特定相互作用发生的，产生二聚体和更高阶的寡聚体。我们发现底物结合使寡聚化平衡向功能性单体蛋白的积累方向移动，这可能是通过隔离稳定伴侣蛋白 - 底物复合物所需的螺旋盖子结构域来实现的。综上所述，这些发现表明伴侣蛋白寡聚化可能作为一种调节伴侣蛋白活性单体形式的可用性以及控制底物结合和释放的机制发挥作用。
Oligomerization in the heat shock protein (Hsp) 70 family has been extensively documented both in vitro and in vivo, although the mechanism, the identity of the specific protein regions involved and the physiological relevance of this process are still unclear. We have studied the oligomeric properties of a series of human Hsp70 variants by means of nanoelectrospray ionization mass spectrometry, optical spectroscopy and quantitative size exclusion chromatography. Our results show that Hsp70 oligomerization takes place through a specific interaction between the interdomain linker of one molecule and the substrate-binding domain of a different molecule, generating dimers and higher-order oligomers. We have found that substrate binding shifts the oligomerization equilibrium towards the accumulation of functional monomeric protein, probably by sequestering the helical lid sub-domain needed to stabilize the chaperone: substrate complex. Taken together, these findings suggest a possible role of chaperone oligomerization as a mechanism for regulating the availability of the active monomeric form of the chaperone and for the control of substrate binding and release.
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影响因子：
4.8
作者：
Buczynski, G;Slepenkov, SV;Witt, SN
通讯作者：
Witt, SN
DOI：
10.1073/pnas.0903503106
发表时间：
2009-05-26
影响因子：
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作者：
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作者：
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影响因子：
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作者：
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