Ubiquitin-interacting motif

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-...

A recent study showed that several APC substrates contain a motif comprising threonine (T), glutamate (E), and lyinse (K) residues that has been termed the TEK-box. " A similar TEK-box is also present around Lysl 1 of uhiquitin. The TEK-box is believed to be a new interaction motif critical for recognizing APC substrates for ubiquitination. It is important to note that TEK-box-containing substrates receive a Kll uhiquitin linkage as... 

The most extensively studied TRIAD is Parkin, shown schematically in Figure 4.5A. The N-terminus contains a region homologous to ubiquitin called the ubiq-uitin domain (UbD), which interacts directly with proteasomes. The C-terminus contains two RING fingers (Rl, R2) separated by a cysteine-rich in-between i ING (IBR) region. This TRIAD motif mediates E3 activity and interacts with molecular chaperones. The last three amino acids of Parkin interact with a PDZ domain and possibly function to anchor Parkin to lipid microdomains. 

Moynihan, T. P., et al., The ubiquitin-conjugating enzymes UbcH7 and UbcH8 interact with RING finger/IBR motif-containing domains of HHARI and H7-AP1./... 

Pringa, E., Martinez-Noel, G., Muller, U., and Harbers, K. Interaction of the ring finger-related U-box motif of a nuclear dot protein with ubiquitin-conjugatmg enzymes. 

Another level of control is mediated through the control of F-box protein stabilities by the SCF complex using an auto-ubiquitination mechanism. Deletion of the F-box motif of various F-box proteins such as yeast Cdc4 or j5-Trcp abolishes the interaction between Skpl/Cull and the F-box proteins [66]. Consequently the F-box proteins become more stable. This regulation may provide a means to recycle the components of SCF complexes between different F-box proteins. In addition, the levels of a particular F-box protein may be in part regulated by the balance between autoubiquitination and substrate-specific ubiquitination and thus could be sensitive to the presence of the substrates. 

The F-box protein family is the largest substrate-recognition subunit family. It enables the eukaryotic cells to use the SCF E3 machinery to ubiquitinate a large number of diverse protein substrates. So far, over 70 F-box proteins have been identified in the human genome [57, 58]. F-box proteins all share an 40-amino acid F-box motif, which is usually followed by a C-terminal protein-protein interaction domain such as the WD40 repeats j5-propeller (Fbw subfamily) and /eucine-rich repeats (LRRs Fbl subfamily Figure 7.5) [59, 60]. F-box proteins interact with... 

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