Ubiquitination

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Ubiquitination is a post-translational modification that involves a small protein called Ubiquitin (Ub) attaching to target proteins, either by monoubiquitination, where there is only one molecule of Ub, or several molecules that form a polyubiquitin chain. This chain can be used to identify proteins that are destined for protein degradation. The ubiquitination mechanism also involves different enzymes that require and rely on energy derived from ATP, which can then be used to form bonds between the Ub protein molecule and the target protein [1]. These enzymes are E1 - the ubiquitin-activating enzyme; E2 - the ubiquitin-conjugating enzyme; and E3 - the ubiquitin protein ligases[2].


The first enzyme, E1, catalyses the stimulation of the ubiquitin which entails the adenylation of the C-terminal carboxylate group on the ubiquitin which then becomes linked to a sulfhydryl group by a thioester bond[3][4]. Upon the activation of the ubiquitin, a pyrophosphate is released from the adenylated C-terminal carboxylate, and the ubiquitin is transferred to a sulfhydryl group in E2[5]. The third enzyme, E3, is then required as a catalyst to enable the transfer of ubiquitin to an ε-amino group which is found on the soon-to-be degraded protein[6].

References

  1. Cell Signalling Technology. Ubiquitin/Proteasome Interactive pathway. 2014 [cited 20/10/17] Available from: https://www.cellsignal.com/contents/science-cst-pathways-ubiquitin-and-ubiquitin-like-proteins/ubiquitin-proteasome-interactive-pathway/pathways-ubiquitin
  2. Berg J, Tymoczko J, Gatto Jr G, Stryer L. Biochemistry. 8th ed. United States of America: W.H. Freeman and Company; 2015; 681-686
  3. Berg J, Tymoczko J, Gatto Jr G, Stryer L. Biochemistry. 8th ed. United States of America: W.H. Freeman and Company; 2015; 681-686
  4. Callis J. The Ubiquitination Machinery of the Ubiquitin System. The Arabidopsis Book. 2014;12e0174
  5. Callis J. The Ubiquitination Machinery of the Ubiquitin System. The Arabidopsis Book. 2014;12e0174
  6. Callis J. The Ubiquitination Machinery of the Ubiquitin System. The Arabidopsis Book. 2014;12e0174
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