TRIM56 coiled-coil domain structure provides insights into its E3 ligase functions

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Biology

Background:

• Protein ubiquitination is a critical post-translational modification essential for cellular regulation.
• E3 ubiquitin ligases, particularly the RING domain family, orchestrate substrate ubiquitination by acting as scaffolds.
• The quaternary structures of RING E3 ligases involved in ubiquitin transfer are not well understood.

Purpose of the Study:

• To elucidate the quaternary structure of the RING E3 ligase TRIM56.
• To understand the structural basis of TRIM56's scaffolding function in ubiquitin transfer.

Main Methods:

• X-ray crystallography was employed to determine the structure of TRIM56.
• Analysis of the coiled-coil domain and RING domain organization within the crystal structure.

Main Results:

• The crystal structure of TRIM56 revealed a tetrameric assembly mediated by its coiled-coil domain.
• This tetramer positions RING domains to form active homodimers, facilitating E2-ubiquitin complex and substrate interaction.
• The C-terminal domains are positioned to recruit substrates to the active sites.

Conclusions:

• The coiled-coil domain-mediated tetramer of TRIM56 serves as a functional scaffold for E3 ligase activity.
• This structural insight explains how TRIM56 facilitates ubiquitin transfer to substrates.
• The findings provide a model for the mechanism of RING E3 ligase-mediated ubiquitination.