Stepwise order in protein complex assembly: approaches and emerging themes

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Cellular processes rely on complex protein nanomachines.
• High-resolution structures reveal machine architecture but not assembly dynamics.
• Co-translational assembly, where subunits interact during translation, is increasingly recognized.

Purpose of the Study:

• To review methodologies for investigating protein complex assembly order.
• To discuss assembly order in the context of specific examples: 20S proteasome, septins, and histone octamer.
• To identify general principles governing multisubunit assembly.

Main Methods:

• Literature review of established and emerging techniques for studying assembly order.
• Analysis of case studies focusing on the 20S proteasome core particle, septin complexes, and histone octamer.
• Comparative analysis of assembly properties across different protein complexes.

Main Results:

• Assembly order is a critical, yet understudied, aspect of protein complex formation.
• Co-translational assembly complicates traditional views of stepwise subunit association.
• Specific examples illustrate diverse assembly pathways and highlight common themes.

Conclusions:

• Understanding assembly order is key to deciphering how cells build complex protein machinery.
• Methodological advancements are essential for further insights into in vivo assembly processes.
• Generalizable principles of assembly order can be derived from studying diverse protein complexes.