A Chaperone Lid Ensures Efficient and Privileged Client Transfer during Tail-Anchored Protein Targeting.
- Author(s): Chio, Un Seng
- Chung, SangYoon
- Weiss, Shimon
- Shan, Shu-Ou
- et al.
Published Web Locationhttps://doi.org/10.1016/j.celrep.2018.12.035
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.
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