Ravindran Madhu Sudhan, Bagchi Parikshit, Inoue Takamasa, Tsai Billy
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
PLoS Pathog. 2015 Aug 5;11(8):e1005086. doi: 10.1371/journal.ppat.1005086. eCollection 2015 Aug.
Mammalian cytosolic Hsp110 family, in concert with the Hsc70:J-protein complex, functions as a disaggregation machinery to rectify protein misfolding problems. Here we uncover a novel role of this machinery in driving membrane translocation during viral entry. The non-enveloped virus SV40 penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol, a critical infection step. Combining biochemical, cell-based, and imaging approaches, we find that the Hsp110 family member Hsp105 associates with the ER membrane J-protein B14. Here Hsp105 cooperates with Hsc70 and extracts the membrane-penetrating SV40 into the cytosol, potentially by disassembling the membrane-embedded virus. Hence the energy provided by the Hsc70-dependent Hsp105 disaggregation machinery can be harnessed to catalyze a membrane translocation event.
哺乳动物胞质Hsp110家族与Hsc70:J蛋白复合物协同作用，作为一种解聚机制来纠正蛋白质错误折叠问题。在此，我们揭示了该机制在病毒进入过程中驱动膜转运的新作用。无包膜病毒SV40穿透内质网（ER）膜到达细胞质，这是一个关键的感染步骤。结合生化、细胞和成像方法，我们发现Hsp110家族成员Hsp105与ER膜J蛋白B14相关联。在这里，Hsp105与Hsc70合作，将穿透膜的SV40提取到细胞质中，可能是通过拆解嵌入膜中的病毒来实现的。因此，由Hsc70依赖的Hsp105解聚机制提供的能量可用于催化膜转运事件。
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