A Chaperone Lid Ensures Efficient and Privileged Client Transfer during Tail-Anchored Protein Targeting
A Chaperone Lid Ensures Efficient and Privileged Client Transfer during Tail-Anchored Protein Targeting
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DOI：
10.1016/j.celrep.2018.12.035
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发表时间：
2019-01-02
期刊：
影响因子：
8.8
通讯作者：
Shan, Shu-ou
中科院分区：
文献类型：
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作者：
Chio, Un Seng;Chung, SangYoon;Shan, Shu-ou
分子伴侣在维持细胞蛋白质稳态中起关键作用。除了防止客户端聚集之外，伴侣通常在网络内中继底物，同时防止路径外的伴侣访问底物。在这里，我们表明，一个保守的盖基序内衬的Get 3 ATP酶的底物结合沟，使这些重要的功能，在有针对性的交付的尾部锚定的膜蛋白（TA）的内质网。该盖防止混杂的TA切换到路径外的伴侣，并且更重要的是，它与Get 4/5支架复合物合作以实现从上游共伴侣Sgt 2到Get 3的快速和特权的TA转移。这些发现提供了一种分子机制，伴侣蛋白在拥挤的胞质环境中维持客户蛋白的通路特异性。
Molecular chaperones play key roles in maintaining cellular proteostasis. In addition to preventing client aggregation, chaperones often relay substrates within a network while preventing off-pathway chaperones from accessing the substrate. Here we show that a conserved lid motif lining the substrate-binding groove of the Get3 ATPase enables these important functions during the targeted delivery of tail-anchored membrane proteins (TAs) to the endoplasmic reticulum. The lid prevents promiscuous TA handoff to off-pathway chaperones, and more importantly, it cooperates with the Get4/5 scaffolding complex to enable rapid and privileged TA transfer from the upstream co-chaperone Sgt2 to Get3. These findings provide a molecular mechanism by which chaperones maintain the pathway specificity of client proteins in the crowded cytosolic environment.