Question

On which residues does ubiquitylation occur? what family of enzymes mediate its addition and its removal?

Answer 1

The addition of ubiquitin to any substrate protein is called ubiquitination. Ubiquitination occur in different ways:

1. It binds to lysine residues through iso-peptide bond

2. Cysteine residues through a thioester bond

3. Serine and threonine residues through an ester bond

4. Amino group of the protein's N-terminus via a peptide bond

The addition of Ubiquitin involves three distinct protein working in a series.

First, E1- Ubiquitin activating enzyme uses the energy of ATP to covalently attach its C-terminal residue to cysteine residue of E1 protein.

Second, Activated ubiquitin is transferred to cysteine residue of another enzyme called E2- Ubiquitin conjugating enzyme.

Finally, ubiquitin is transferred to substrate protein by another enzyme called E3- ubiquitin ligase.

In vertebrates, there are two types of E1, fifty types of E2 and, several hundred types of E3 ligages present.

Deubiquitinases (DUBs) is the enzyme which mediate the removal of ubiquitin. Approximately, 80 DUBs are known in human genome. This enzyme mediate the lysis of bond between lysine of protein substrate protein and C terminal residue of ubiquitin.