E3 ubiquitin ligases are the matchmakers in the ubiquitination cascade. Hect domain type e3 ligases will have one more transthiolation reaction to transfer the ubiquitin molecule. Photocrosslinking activitybased probes for ubiquitin ring. Ubiquitin ligases and beyond bmc biology full text. The rpn10 cterminal razul is intrinsically disordered left panel, but folds to form a 4helix bundle with the azul domain of e3 ligase e6ap green, thus recruiting e6ap to the proteasome. Regulation of e3 ubiquitin ligases by homotypic and heterotypic. Mutation of these residues abolished the preferential interaction between the ring domain and ubiquitinloaded e2 and abrogated ubiquitin e3 ligase activity. Recognition of substrate degrons by e3 ubiquitin ligases and modulation by smallmolecule mimicry strategies pdf. Hect and ring finger families of e3 ubiquitin ligases at a glance. E2 is the ubiquitin conjugating enzyme, to which the ubiquitin is transferred from the e1. The activity of most e3s is specified by a ring domain, which binds to an e2. C schematic representation of an rbrtype ubiquitin e3 ligase.
Currently, e3 ligases can be classified in three main types depending on the presence of characteristic domains and on the mechanism of ubiquitin transfer to the substrate protein. In arabidopsis thaliana, the ringtype e3 ubiquitin ligase family, named rglg ring domain ligase, is composed of five members, i. Members of the ring finger ubiquitin ligase family can function as monomers, dimers or. How to inactivate human ubiquitin e3 ligases by mutation frontiers. A new scheme to discover functional associations and regulatory. This backbone tracing was made from protein data bank file 1jsq 120.
E3 ligases confer specificity to ubiquitination by recognizing target substrates and mediating transfer of ubiquitin from an e2 ubiquitinconjugating enzyme to substrate. Several protein domains, including the ubiquitinassociated. Protein ubiquitination catalyzed by e3 ubiquitin ligases play important. Regulation of e3 ubiquitin ligases by homotypic and heterotypic assembly. The crystal structure of the free hect domain of e6ap suggests that it. Atpub18 and atpub19 are homologous ubox e3 ubiquitin ligases in arabidopsis arabidopsis thaliana. Mechanism of ubiquitylation by dimeric ring ligase rnf4 europe. A ubiquitin ligase is a protein that recruits an e2 ubiquitinconjugating enzyme that has been. Ubiquitin ligases rglg1 and rglg5 regulate abscisic acid.
The activity of most e3s is specified by a ring domain, which binds to an e2 approximately ubiquitin thioester and activates discharge. Ring e3s ring e3s are the most abundant type of ubiquitin ligases. Individual poster panels are available as jpeg files at. The e3 therefore determines the substrate specificity of ubiquitination, and the diversity of the cellular functions of. Roles of four arabidopsis ubox e3 ubiquitin ligases in. An external file that holds a picture, illustration, etc. For the e3 ligases of the homologous to the e6ap carboxyl terminus hect domain family.
Two ring domains are separated by an inbetweenring ibr domain. Here, lossoffunction and overexpression tests identified atpub18 as a negative regulator in abamediated stomatal closure and water stress. Structure of e3 ligase e6ap with a proteasomebinding site. Activitybased probes abps are valuable research tools for studying enzyme function. Ubiquitin e3 ligases are one of the largest enzyme families yet abps for this enzyme class do not exist.
E3 ligases confer specificity to ubiquitination by recognizing target substrates and mediating. Rnabinding ubiquitin ligases are also found in other eukaryotes, but the link to mrna regulation currently. Atpub19 is a negative regulator of abscisic acid mediated drought responses, whereas the role of atpub18 in drought responses is unknown. E3 ubiquitin ligases are key components of the enzymatic machinery catalyzing the. Rglg1 and rglg2 have been reported to affect hormone signaling, since the rglg1 rglg2 double mutant shows altered auxin and cytokinin levels yin et al.
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