With a predicted molecular weight of 68 kDa, octa-Ubiquitin chains are composed of eight Ubiquitin monomers, which are covalently linked through isopeptide bonds that typically form between a lysine residue of one Ubiquitin molecule and the C-terminal glycine residue of another Ubiquitin molecule (1). Each human Ubiquitin monomer is 76 amino acids (aa) in length and shares 96% and 100% aa identity with yeast and mouse Ubiquitin, respectively (2). Seven of the 76 aa in Ubiquitin are lysine residues that can participate in poly-Ubiquitin chain formation. Linkage through each of the lysine residues is thought to serve as a signal that affects protein degradation, signaling, trafficking, and other cellular processes (3-8).
Linkage specific octa-Ub can be used to investigate mechanism of binding and recognition by E1 or E2 enzymes, deubiquitinating enzymes, E3 ligases, the proteasome or other proteins that contain Ubiquitin-associated domains (UBAs) or Ubiquitin-interacting motifs (UIMs). This product is formed with wild-type Ubiquitin and linkage-specific enzymes. It has been shown that the rate of Ubiquitin-substrate conjugate degradation is related to poly-Ubiquitin chain length. Tetra-Ubiquitin is the minimal unit required for recognition by the proteasome, and longer chains probably have enhanced binding to proteasomal subunits and may be more resistant to disassembly by a proteasome-associated isopeptidases.
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