The carboxy-terminal domain of Hsc70 provides binding sites for a distinct set of chaperone cofactors
The carboxy-terminal domain of Hsc70 provides binding sites for a distinct set of chaperone cofactors
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DOI：
10.1128/mcb.18.4.2023
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发表时间：
1998-04-01
影响因子：
5.3
通讯作者：
Höhfeld, J
中科院分区：
文献类型：
--
作者：
Demand, J;Lüders, J;Höhfeld, J
哺乳动物细胞中热休克同源Hsc 70蛋白的伴侣活性的调节涉及与伴侣辅因子的合作，所述辅因子例如Hsp 40; BAG-1; Hsc 70相互作用蛋白，Hip;和Hsc 70-Hsp 90-organizing protein，Hop，通过酵母双杂交系统和体外相互作用试验，我们已经提供了对Hsc 70与不同辅因子合作的结构基础的深入了解。Hsc 70的羧基末端结构域，以前显示在伴侣蛋白的肽结合口袋上形成盖子，介导Hsc 70与Hsp 40和Hop的相互作用。值得注意的是，这两种辅因子以非竞争性方式结合到Hsc 70的羧基末端，揭示了在该结构域内存在Hsp 40和Hop的不同结合位点。相反，Hip仅与Hsc 70的氨基末端ATP酶结构域相互作用。Hsc 70具有单独的Hsp 40、Hip和Hop的非重叠结合位点，这似乎使得伴侣蛋白能够与多种辅因子同时合作。另一方面，BAG-I和Hip最近已显示竞争结合ATP酶结构域，因此，我们的数据建立了一个网络的合作和竞争的辅因子调节Hsc 70在哺乳动物细胞中的伴侣活性的存在。
The modulation of the chaperone activity of the heat shock cognate Hsc70 protein in mammalian cells involves cooperation with chaperone cofactors, such as Hsp40; BAG-1; the Hsc70-interacting protein, Hip; and the Hsc70-Hsp90-organizing protein, Hop, By employing the yeast two-hybrid system and in vitro interaction assays, we have provided insight into the structural basis that underlies Hsc70's cooperation with different cofactors, The carboxy-terminal domain of Hsc70, previously shown to form a lid over the peptide binding pocket of the chaperone protein, mediates the interaction of Hsc70 with Hsp40 and Hop, Remarkably, the two cofactors bind to the carboxy terminus of Hsc70 in a noncompetitive manner, revealing the existence of distinct binding sites for Hsp40 and Hop within this domain, In contrast, Hip interacts exclusively with the aminoterminal ATPase domain of Hsc70, Hence, Hsc70 possesses separate nonoverlapping binding sites for Hsp40, Hip, and Hop, This appears to enable the chaperone protein to cooperate simultaneously,vith multiple cofactors, On the other hand, BAG-I and Hip have recently been shown to compete in binding to the ATPase domain, Our data thus establish the existence of a network of cooperating and competing cofactors regulating the chaperone activity of Hsc70 in the mammalian cell.