Ubiquitin interaction

Figure 5.9. Split ubiquitin as a sensor for protein-protein interactions. Protein A is fused to the N-terminal domain and protein B is fused to the C-terminal domain of ubiquitin. Interaction of A and B reconstitutes a full-sized, folded ubiqutin. The folded ubiquitin is recognized by a specific protease and cleavage releases the reporter protein.

Hofmann, K. and Falquet, L. A ubiquitin-interacting motif conserved in components of the proteasomal and lysosomal protein degradation systems. Trends Biochem Sci 2001, 26, 347-50. 

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-...

Positions that in the Vps27 structure [79] have contact with ubiquitin are labelled by asterisks in the top line. (B) The bottom panel shows an alignment of representative GAT-domain members. Only the last helix, which contains the ubiquitin-interaction site, is depicted. 

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. 

Fig. 12.7. Domain scheme of selected parkin-like ubiquitin ligases. Black boxes represent the ubiquitin-interacting domains discussed in the text. The three gray boxes labeled FI, F2 and F3 represent the triad of RINC-finger like...

D. R., and Sundquist, W. I., Structure and ubiquitin interactions of the conserved zinc finger domain of Npl4, J. Biol. Biol, 2003, 278, 20225. 

Ubiquitin interacts avidly but not covalently with ABP and such complexes can be isolated from AD brain extracts (276). Ubiquitin and APP colocalize to endosome-lysosomes implicated in APP proteolysis (277). A clear link between defective APP processing and the ubiquitin-proteasome system was demonstrated by Chen et al. 

Ubiquitin Interaction with the Tollip C2 and CUE domains and PtdIns(3)P 124... 

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