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. 2021 Nov 11;10:e72798. doi: 10.7554/eLife.72798

Figure 7. A model for how UCH37 promotes substrate processing and recycling of the proteasome through debranching of polyUb chains.

Figure 7.

(A) A schematic of singly capped 26S proteasome in s1 state (PDB code: 4CR2) with locations indicated for intrinsic Ub receptors (RPN1, RPN10, and RPN13) and associated DUBs (RPN11 and UCH37); for clarity, USP14 is not shown. (B) RAD23 delivers a substrate (brown) modified by polyUb with a single branch point. UCH37 binds both distal Ubs at the branch point. K48-linked Ubs are shown in yellow whereas a non-K48-linked Ub is shown in white. (C) A substrate-engaged proteasome (PDB code: 4CR4) where substrate starts to be translocated and polyUb is removed en bloc by RPN11. Whether debranching by UCH37 occurs before or after RPN11 action is unknown. (D) UCH37 cleavage of the K48 linkage at the branch point facilitates release of free (poly)Ub chains and the shuttle factors.