Chemical proteomics for subcellular proteome analysis

Area of Science:

• Proteomics
• Cell Biology
• Chemical Biology

Background:

• Protein function is regulated by subcellular localization and dynamic changes.
• Chemical proteomics provides efficient profiling of protein features in native cellular environments.

Purpose of the Study:

• To review recent advancements in subcellular-compartment-focused chemical proteomics.
• To discuss methods that avoid organelle fractionation for proteome analysis.

Main Methods:

• Organelle-specific activity-based protein profiling (ABPP).
• Engineered ascorbate peroxidase (APEX) for proteome analysis within organelles.
• Organelle-localizable reactive molecules (ORMs) for selective protein tagging.
• Conditional proteomics for elucidating zinc homeostasis.

Main Results:

• ABPP and APEX enable proteome analysis within organelles and sub-organelles.
• ORMs selectively tag nuclear and mitochondrial proteins in various biological samples.
• Conditional proteomics identifies proteins in Zn2+-rich cellular spaces.

Conclusions:

• Subcellular-compartment-focused chemical proteomics offers powerful tools for studying protein localization and function.
• These methods are applicable to diverse biological systems, including primary neurons and brain slices.