Protein Degradation through Ubiquitination – Oxford University Press (2014)

What happens when a protein is “done” and must be taken care of? The companion animation to the Oxford University Press text book Molecular Biology- Principles of Genome Function, encapsulates the basics of ubiquitination through E1>E2>E3 cascade and the molecular components involved. Ubiquitin is a small protein that can be covalently linked to lysine residues of proteins targeted for degradation by proteosomes inside the cell.

E1 activating enzyme
E2 conjugating enzyme
E3 ligase complex

The combinatorial diversity of E3 complexes with with other protein subunits binding to N and C-temini of the backbone protein Cullen leads to a very rich repertoire of protein targeting enzymes:

ROC1–CUL1–SKiP/F-box
ROC1–CUL2–elonginB/C–VHL-box/SOCS-box
ROC1–CUL3–BTBdomain-containing-proteins
ROC1–CUL4–DDB1
ROC2–CUL5–ElongingB/C–VHL-box/SOCS-box

For instance, the well known breast and ovarian cancer susceptibility gene BRCA1 is a key component of E3 ubiquitin ligase and its impairment leads to cancer. It is involved in the ROC1–CUL1–SKiP/F-box type of E3 ligases.

In plants, the growth hormone auxin perception is possible through ROC1–CUL1–SKiP/F-box E3 ligase complex.

Another E3 ligase is involved in damaged DNA repair response through DNA damage-binding protein 1 (DDB1) subunit.

There are many diverse functions of the E1>E2>E3 ubiquitination cascade and this animation provides a simplified bare backbone view of the molecular complexes.