Prion-specific Hsp40 function: The role of the auxilin homolog Swa2.
Prion-specific Hsp40 function: The role of the auxilin homolog Swa2.
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DOI：
10.1080/19336896.2017.1331810
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发表时间：
2017-05-04
期刊：
影响因子：
2.3
通讯作者：
Hines JK
中科院分区：
文献类型：
--
作者：
Oliver EE;Troisi EM;Hines JK
酵母朊病毒是一种以蛋白质为基础的遗传因子，通过母细胞到子细胞的胞质转移在细胞群中繁殖。包括Hsp 70、Hsp 40/J蛋白Sis 1和Hsp 104在内的分子伴侣蛋白是朊病毒持续繁殖所必需的，然而，对于各种朊病毒，对伴侣蛋白的具体要求不同。我们最近报道，Swa 2，酵母同系物的哺乳动物蛋白生长素，是专门需要的朊病毒的繁殖[URE 3]。[URE 3]繁殖需要Swa 2的功能性J结构域和四方三肽重复（TPR）结构域，但不需要Swa 2网格蛋白结合。我们的结论是TPR结构域决定了Swa 2和[URE 3]之间遗传相互作用的特异性，并且该结构域可能与一种或多种具有C-末端EEVD基序的蛋白质相互作用。在这里，我们扩展了分析，以纳入支持这一假设的其他数据。我们还提出了新的数据消除热休克蛋白104作为相关的Swa 2结合伙伴，并讨论我们的研究结果的背景下，最近的其他工作涉及热休克蛋白90。基于这些研究结果，我们提出了一个新的模型Swa 2参与[URE 3]的传播，其中Swa 2和Hsp 90介导的多蛋白复合物的形成，增加了可用于Hsp 104解聚的位点的数量。
Yeast prions are protein-based genetic elements that propagate through cell populations via cytosolic transfer from mother to daughter cell. Molecular chaperone proteins including Hsp70, the Hsp40/J-protein Sis1, and Hsp104 are required for continued prion propagation, however the specific requirements of chaperone proteins differ for various prions. We recently reported that Swa2, the yeast homolog of the mammalian protein auxilin, is specifically required for the propagation of the prion [URE3]. [URE3] propagation requires both a functional J-domain and the tetratricopeptide repeat (TPR) domain of Swa2, but does not require Swa2 clathrin binding. We concluded that the TPR domain determines the specificity of the genetic interaction between Swa2 and [URE3], and that this domain likely interacts with one or more proteins with a C-terminal EEVD motif. Here we extend that analysis to incorporate additional data that supports this hypothesis. We also present new data eliminating Hsp104 as the relevant Swa2 binding partner and discuss our findings in the context of other recent work involving Hsp90. Based on these findings, we propose a new model for Swa2's involvement in [URE3] propagation in which Swa2 and Hsp90 mediate the formation of a multi-protein complex that increases the number of sites available for Hsp104 disaggregation.