Ubiquitin evolution

Hochsteassee, M. Evolution and function of ubiquitin-like protein-conjugation systems, Nat Cell Biol 2000, 2, E153-157. 

Increasing evidence suggests that evolution has used (and is using) the E2 fold for new purposes. In one apparent example of functional expansion, E2 core domains have been observed to be embedded within much larger polypeptide chains [140, 141]. The functional properties of these massive E2s remain poorly characterized, and it is likely that more of them will be discovered. But the clearest case of functional diversification is provided by the UEV proteins. UEVs are related to E2s in their primary, secondary, and tertiary structures, but they lack an active-site cysteine residue and therefore cannot function as canonical E2s [142]. Nonetheless they play several different roles in ubiquitin-dependent pathways. 

While the functional analogy between ThiS, MoaD, and ubiquitin-like modifiers is widely accepted, the two protein classes are frequently described as unrelated sometimes even a convergent evolution to the energetically favorable ubiquitin fold is discussed. Despite these claims, there is a statistically significant sequence... 

Finally, it should be mentioned that there are a number of protein domains that have some structural resemblance to ubiquitin, although a sequence similarity cannot be established - not even by the most sophisticated methods available today. It cannot be excluded that there are true instances of convergent evolution among these cases. However, it appears more likely that these proteins and domains represent distant members of the ubiquitin superfamily, which have undergone a fundamental change of function and no longer need to conserve sequence positions that are considered hallmarks of ubiquitin-like molecules. In particular three domain classes should be mentioned in this context. The PERM domain (4.1, ezrin,... 

When analyzing proteins of the ubiquitin system from a genomic perspective, there are a number of interesting examples where in the course of evolution one... 

As has been clearly demonstrated, pi05 has two distinct ubiquitin system targeting motifs, an acidic domain that contains also the Lys residues essential for ubiquitin anchoring, and a C-terminal phosphorylation/E3-binding domain. An important, yet unresolved, question involves the biological rationale behind the evolution of these two sites. To resolve this... 

Fig. C11.5 Three examples of knots in proteins, including the very complex knot 5i in a protein called human ubiquitin hydrolase (the rightmost image). In each case, a simple model of sticks shows the same knot as in the protein. To help the eye, each chain is colored in rainbow colors from one end to the other. The figure is reproduced, with kind permission by the authors, from the paper P. Virnau, L. Mirny and M. Kardar, Intricate Knots in Proteins Function and Evolution, PLoS Computational Biology, v. 2, pp. 1074-1079, 2006.

Segev, E. Wyttenhach, T. Bowers, M. T. Gerber, R. B. Conformational evolution of ubiquitin ions in electrospray mass spectrometry Molecular dynamics simulations at gradually increasing temperatures. Phys. Chem. Chem. Phys. 2008,10, 3077-3082. 

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