Exchangeable chaperone modules contribute to specification of type I and type II Hsp40 cellular function
Exchangeable chaperone modules contribute to specification of type I and type II Hsp40 cellular function
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DOI：
10.1091/mbc.e03-03-0146
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发表时间：
2004-02-01
影响因子：
3.3
通讯作者：
Cyr, DM
中科院分区：
文献类型：
--
作者：
Fan, CY;Lee, S;Cyr, DM
Hsp40家族成员调节Hsp70结合标准多肽的能力，从而在细胞生理学中发挥重要作用。I型和II型Hsp40，如酵母Ydj1和Sis1，与胞质Hsp70 Ssa 1形成分子伴侣对，以不同的效率折叠蛋白质并执行特定的细胞功能。Ydj1和Sis1指定Hsp70功能的机制尚不清楚。Ydj 1和Sis 1在其氨基和羧基末端具有高度的序列同一性，但各自包含一个结构独特且位于中心的蛋白模块，该模块与伴侣功能有关。为了测试Ydj1和Sis1的伴侣蛋白模块是否在Hsp70作用的特化中起作用，我们构建了一组嵌合Hsp40，其中Ydj1和Sis1的伴侣蛋白结构域被交换以形成YSY和YS2。纯化后的Ydj1和YSY分别具有与Ydj1和Sis1相似的蛋白折叠活性和底物特异性。在体内研究中，YSY表现出功能的获得，并且与Ydj1不同，可以补充sis1 Delta的致死表型并促进朊病毒[RNQ+]的维持。Ydj1和Sis1含有可交换的分子伴侣模块，有助于Hsp70功能的规范。
Hsp40 family members regulate Hsp70s ability to bind normative polypeptides and thereby play an essential role in cell physiology. Type I and type II Hsp40s, such as yeast Ydj1 and Sis1, form chaperone pairs with cytosolic Hsp70 Ssa1 that fold proteins with different efficiencies and carry out specific cellular functions. The mechanism by which Ydj1 and Sis1 specify Hsp70 functions is not clear. Ydj1 and Sis1 share a high degree of sequence identity in their amino and carboxyl terminal ends, but each contains a structurally unique and centrally located protein module that is implicated in chaperone function. To test whether the chaperone modules of Ydj1 and Sis1 function in the specification of Hsp70 action, we constructed a set of chimeric Hsp40s in which the chaperone domains of Ydj1 and Sis1 were swapped to form YSY and SYS. Purified SYS and YSY exhibited protein-folding activity and substrate specificity that mimicked that of Ydj1 and Sis1, respectively. In in vivo studies, YSY exhibited a gain of function and, unlike Ydj1, could complement the lethal phenotype of sis1Delta and facilitate maintenance of the prion [RNQ+]. Ydj1 and Sis1 contain exchangeable chaperone modules that assist in specification of Hsp70 function.