TRIM21 and Fc-engineered antibodies: decoding its complex antibody binding mode with implications for viral...

Area of Science:

• Immunology
• Structural Biology
• Virology

Background:

• TRIM21 is a key immune protein regulating antibody-mediated responses.
• Understanding TRIM21's interaction with antibodies is crucial for antiviral immunity.

Purpose of the Study:

• To investigate the interaction between TRIM21 and Fc engineered antibodies.
• To elucidate the mechanisms of TRIM21-mediated viral neutralization and degradation.

Main Methods:

• Biosensor assays
• Mass photometry
• Electron microscopy
• Structure prediction

Main Results:

• TRIM21's viral degradation capacity depends on Fc region affinity and avidity.
• A novel bivalent binding mechanism was identified, enhancing TRIM21's interaction with antibodies.
• TRIM21 exhibits a dual role in recognizing and degrading antibody-coated viruses.

Conclusions:

• TRIM21's unique binding mode is critical for antiviral defense.
• Findings provide insights for developing novel antiviral therapies leveraging TRIM21.
• The study advances understanding of intracellular immune responses and effector functions.