Ubiquitin core domain

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. 

The C terminus of p53 contains a basic domain where DNA can be bound in a nonspecific way. Furthermore, the C-terminal domain contains several sites for post-translational modifications, including Ser-phosphorylation, Lys-acetylation, ubiquitination, and Lys-sumoylation. Futhermore, sequence signals for nuclear localization, sequence sections for tetramerization, and binding sites for transcription factors are found in the C-terminal part. Overall, the C-terminal domain has an important function for the regulation of p53. There is experimental evidence that specific DNA binding of the core domain is controlled by phosphorylation of the C-terminal domain. 

Skpl serves as an adaptor protein that provides a molecular link between Cull/ Rod and the F-box proteins [4, 5]. The Skpl protein contains two separate protein-interaction domains that are conserved among its family members between species [21]. The N-terminal region of Skpl (- l-70 a.a.) interacts with Cull while the C-terminal half (100-163 a.a.) binds the F-box proteins [21]. The use of Skpl as an adaptor to link the core ubiquitin E3 ligase components of Cull/Rocl with numerous and diverse substrate-targeting subunits, the F-box proteins, represents a strategy to specifically target many proteins for ubiquitination... 

Fig. 1. Histone modifications on the nucleosome core particle. The nucleosome core particle showing 6 of the 8 core histone N-terminal tail domains and 2 C-terminal tails. Sites of post-translational modification are indicated by coloured symbols that are defined in the key (lower left) acK = acetyl lysine, meR = methyl arginine, mcK = methyl lysine, PS = phosphoryl serine, and uK = ubiquitinated lysine. Residue numbers are shown for each modification. Note that H3 lysine 9 can be either acetylated or methylated. The C-terminal tail domains of one H2A molecule and one H2B molecule are shown (dashed lines) with sites of ubiquitination at H2A lysine 119 (most common in mammals) and H2B lysine 123 (most common in yeast). Modifications are shown on only one of the two copies of histones H3 and H4 and only one tail is shown for H2A and H2B. Sites marked by green arrows are susceptible to cutting by trypsin in intact nucleosomes. Note that the cartoon is a compendium of data from various organisms, some of which may lack particular modifications e.g., there is no H3meK9 in S. cerevisiae. (From Ref [7].)...

Histones within transcriptionally active chromatin and heterochromatin also differ in their patterns of covalent modification. The core histones of nucleosome particles (H2A, H2B, H3, H4 see Fig. 24-27) are modified by irreversible methylation of Lys residues, phosphorylation of Ser or Thr residues, acetylation (see below), or attachment of ubiquitin (see Fig. 27-41). Each of the core histones has two distinct structural domains. A central domain is involved in histone-histone interaction and the wrapping of DNA around the nucleosome. A second, lysine-rich amino-terminal domain is generally positioned near the exterior of the assembled nucleosome particle the covalent modifications occur at specific residues concentrated in this amino-terminal domain. The patterns of modification have led some researchers to propose the existence of a histone code, in which modification patterns are recognized by enzymes that alter the structure of chromatin. Modifications associated with transcriptional activation would be recognized by enzymes that make the chromatin more accessible to the transcription machinery. 

The biologic function of Ras is mediated by its ability to activate downstream cytoplasmic signaling networks through binding to a panel of effector proteins. The Ras-effector interaction is mediated through interactions between the core effector domain (amino acids 32 0) of Ras (see Fig. 2) and the specific residues within the Ras-binding domain (RBD) or Ras-association domain (RA) found in most Ras effector proteins. The RBDs and RA domains of effector proteins do not exhibit primary sequence homology, but instead they share a common tertiary structure that consists of an ubiquitin superfold, which forms critical contacts with Ras (33). 

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