Co-translational assembly of mammalian nuclear multisubunit complexes

Area of Science:

• Molecular Biology
• Cell Biology
• Structural Biology

Background:

• Cells expend considerable energy constructing multiprotein assemblies with precise subunit ratios.
• The genomic dispersion of genes for subunits in eukaryotic multisubunit complexes raises questions about their assembly mechanisms.

Purpose of the Study:

• To investigate the assembly process of large mammalian nuclear transcription complexes.
• To determine the role of dimerization domains in directing co-translational assembly pathways.
• To elucidate the link between protein synthesis and complex assembly in mammalian cells.

Main Methods:

• Co-translational assembly assays for mammalian nuclear transcription complexes (TFIID, TREX-2, SAGA).
• Analysis of dimerization domains and their influence on assembly kinetics (simultaneous vs. sequential).
• Assessment of protein degradation resulting from failed co-translational interactions.

Main Results:

• Mammalian nuclear transcription complexes assemble co-translationally.
• Dimerization domain position and type dictate simultaneous or sequential assembly.
• Failure in co-translational interaction leads to partner protein degradation.

Conclusions:

• Protein synthesis and complex assembly are intrinsically linked in mammalian cells.
• Co-translational assembly is a key mechanism to prevent non-specific interactions and protein aggregation.
• Findings provide insights into endogenous co-translational building blocks for structural biology.