Difference between revisions of "Part:BBa K4165001"

Revision as of 17:29, 4 October 2022

Truncated tripartite motif-containing 21 (TRIM21)

E3 ligase which participates in the ubiquitination cascade and degradation by proteasome 26s.

Assembly Compatibility:

10
COMPATIBLE WITH RFC[10]
12
COMPATIBLE WITH RFC[12]
21
COMPATIBLE WITH RFC[21]
23
COMPATIBLE WITH RFC[23]
25
COMPATIBLE WITH RFC[25]
1000
INCOMPATIBLE WITH RFC[1000]
Illegal BsaI.rc site found at 514

Usage and Biology

Tripartite motif-containing 21 (TRIM21) is an E3 ubiquitin ligase that has a strong affinity for the Fc domain of antibodies. It is mainly composed of four domains (RING domain, B-box domain, coiled-coil domain, and PRYSPRY antibody-binding region). TRIM21 engages the ubiquitin-proteasome system to destroy antibody-bound pathogens during infection. 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 manner. 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.

                            Figure 1.: A graphical illustration showing the domains of TRIM21.

Features

Ring-Domain: This part is responsible for the dimerization and activation of Trim21.

B-Box Domain: This domain exerts a regulatory role through interaction with ring domains as it drives the self-assembly of oligomers, bringing together multiple RING domains, which may facilitate RING dimerization.

Coiled-coil Domain: This domain undergoes monomer–dimer exchange to allow homodimerization of TRIM.

References

1. Clift, D., McEwan, W. A., Labzin, L. I., Konieczny, V., Mogessie, B., James, L. C., & Schuh, M. (2017). A Method for the Acute and Rapid Degradation of Endogenous Proteins. Cell, 171(7), 1692-1706.e18. https://doi.org/10.1016/j.cell.2017.10.033

2. D.L. Mallery, W.A. McEwan, S.R. Bidgood, G.J. Towers, C.M. Johnson, L.C. James Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21) Proc. Natl. Acad. Sci. USA, 107 (2010), pp. 19985-19990

3. Kleiger, G., & Mayor, T. (2014). Perilous journey: a tour of the ubiquitin-proteasome system. Trends in cell biology, 24(6), 352. https://doi.org/10.1016/j.tcb.2013.12.003

4. L.C. James, A.H. Keeble, Z. Khan, D.A. Rhodes, J. Trowsdale Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function Proc. Natl. Acad. Sci. USA, 104 (2007), pp. 6200-

5. Zhang, Y., Li, L., Munir, M., & Qiu, H. (2018). RING-Domain E3 Ligase-Mediated Host–Virus Interactions: Orchestrating Immune Responses by the Host and Antagonizing Immune Defense by Viruses. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2018.01083

@@ Line 22: / Line 22: @@
 Ring-Domain: This part is responsible for the dimerization and activation of Trim21.
-B-Box Domain: This domain drives the self-assembly of oligomers, bringing together multiple RING domains, which may facilitate RING dimerization.
+B-Box Domain: This domain exerts a regulatory role through interaction with ring domains as it drives the self-assembly of oligomers, bringing together multiple RING domains, which may facilitate RING dimerization.
+Coiled-coil Domain: This domain undergoes monomer–dimer exchange to allow homodimerization of TRIM.
 ===References===