Other Ubiquitin-binding Domains

In addition to the well-established and widely distributed ubiquitin-interaction domains described above, there are several other domains with a more limited scope or with binding properties that are just beginning to be uncovered. Two interesting candidates are the NZF and ZnF-UBP/PAZ domains. 

Obviously, not all proteins known to interact with ubiquitin or ubiquitin-like domains contain one of the professional ubiquitin-interaction domains. RptS and Rpnl, two subunits of the proteasome that bind to ubiquitin and UbLs, respectively, do not belong to any of the classes described above. Most probably, a large number of uncharacterized proteins with high affinity and specificity for ubiquitin are still waiting to be discovered. The bioinformatical tools described in the early sections of this chapter will be instrumental for this task. 

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The same regions appear to be important for interactions of ubiquitin with many other DUBs (see Figure 8.2) and Ub-binding proteins. Importantly, all ubiquitin-binding domains examined utilize these same surfaces in binding ubiquitin. 

Fig. 12.1. Domain scheme of selected proteins with internal ubiquitin-like domains. Ubiquitin-like domains are indicated by black boxes. Other domains are abbreviated as follows ThiF, NAD-binding domain in ubiq-uitin activating enzymes UAct, 2nd conserved domain in ubiquitin activating enzymes ...

Figure 12.4A shows the interaction of the first CUE domain of Cue2 interacting with ubiquitin, which might serve as a general model for the interaction mode of other UBA-like domains. The CUE domain binds to the Ile-44 patch of ubiquitin, in accordance with the chemical shift perturbation results of the UBA ubiquitin interaction [52], On the side of the CUE domain, residues of the first and third helix participate in this interaction surface. These residues include the Phe-Pro and Leu-Leu motifs, which had been predicted to be important for ubiquitin binding, based on comparative sequence analysis of CUE-A and CUE-B domains [62]. Positions in close contact with ubiquitin are also indicated in the alignment of Figure 12.3. The two available structures of the CUE ubiquitin complexes offer little expla-...

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