Engineered Proteins and Chemical Tools to Probe the Cell Surface Proteome

Area of Science:

• Proteomics
• Cell Biology
• Biochemistry

Background:

• The cell surface proteome (surfaceome) is crucial for cellular communication and interaction.
• Despite its importance, fewer than 50 cell surface proteins are targeted by approved drugs.
• Disease-associated alterations in the surfaceome represent a largely untapped reservoir for therapeutic targets.

Purpose of the Study:

• To review the unique characteristics and functions of the surfaceome.
• To provide an overview of current and emerging surfaceomics methods for target discovery.
• To highlight the role of surfaceome research in identifying novel therapeutic targets, particularly neo-epitopes.

Main Methods:

• Specialized labeling, enrichment, and proteomic approaches for surfaceome analysis.
• Proximity labeling proteomics (PLP) techniques (enzymatic and photoaffinity) to map cell surface interactions.
• Analysis of extracellular post-translational modifications (PTMs) including glycosylation and proteolytic remodeling.
• Identification of tumor-specific peptide-MHC complexes.

Main Results:

• Surfaceomics enables the measurement of protein expression changes on the cell surface.
• PLP methods effectively map protein-protein interactions and membrane complexes at the cell surface.
• Extracellular PTMs and the secretome play significant roles in cell surface regulation.
• Identification of neo-protein epitopes, including PTMs and complexes, is advancing therapeutic development.

Conclusions:

• Surfaceomics is essential for understanding cell surface biology and identifying novel therapeutic targets.
• Advanced proteomic techniques are critical for dissecting the complexity of the surfaceome.
• The identification of disease-associated neo-epitopes on the cell surface holds significant promise for future therapies.