Part:BBa_K4165001

Truncated tripartite motif-containing 21 (TRIM21)

Usage and Biology

Tripartite motif-containing 21 (TRIM21) is an E3 ubiquitin ligase that has a strong affinity for the Fc domain of antibodies1,2. It is mainly composed of four domains (RING domain, B box domain, coiled-coil domain, and PRYSPRY antibody-binding region).5 TRIM21 engages the ubiquitin-proteasome system to destroy antibody-bound pathogens during infection.1,4 In our project, we used the truncated version of Trim21 proposed by team NUDT 2020 BBa_K3396007, they replaced the ‘PRYSPRY’ region with a protein pair (Protac), one of the pair will be fused to Trim21 and the other to our tau binding peptide, resulting in targeting and degradation of tau upon binding of the Protac.

A highly conserved, 76 amino acid polypeptide called ubiquitin must first be activated by an E1 enzyme in an ATP-dependent way. The E1 binds ubiquitin's C-terminal end to a cysteine residue in its active site through a covalent connection. The E2 or ubiquitin-conjugating enzyme is the second enzyme in the cascade to receive the thioesterified ubiquitin from the E1 active site. Finally, The E3 ubiquitin ligase then promotes the transfer of ubiquitin onto the substrate by binding to both the protein substrate and the E2-bound ubiquitin.3