Figure 1.

Substrate Specificity Is Controlled by Binding Pockets in DUBs

The specificity of DUBs for differently linked Ub chains and ubiquitylated substrates is governed by specific binding pockets.

(A) Overview of different pockets that may govern specificity in polyUb chain recognition and processing.

(B) Overview of binding pockets that may play a role in recognition and processing of (poly)ubiquitylated substrates.

(C) Tools to study the binding and processing of DUBs using the various Ub-binding sites. I, mUb probe/substrate, targeting the S1 pocket; II, isopeptide warhead-containing diUb probes or differently linked diUb substrates, to study S1-S1′ pockets; III, C-terminally reactive diUb-based probes/substrates, targeting S1-S2 pockets, as described in this article. When discussing free Ub chains or diUbs, the most C-terminal Ub in a chain is referred to as proximal and the most N-terminal Ub as distal. The active site reactive element/reporter molecule is depicted as a red triangle.