Introduction: Cell-surface proteins are extremely important for many cellular events, such as regulating cell-cell communication and cell-matrix interactions. Aberrant alterations in surface protein expression, modification (especially glycosylation), and interactions are directly related to human diseases. Systematic investigation of surface proteins advances our understanding of protein functions, cellular activities, and disease mechanisms, which will lead to identifying surface proteins as disease biomarkers and drug targets.
Areas covered: In this review, we summarize mass spectrometry (MS)-based proteomics methods for global analysis of cell-surface proteins. Then, investigations of the dynamics of surface proteins are discussed. Furthermore, we summarize the studies for the surfaceome interaction networks. Additionally, biological applications of MS-based surfaceome analysis are included, particularly highlighting the significance in biomarker identification, drug development, and immunotherapies.
Expert opinion: Modern MS-based proteomics provides an opportunity to systematically characterize proteins. However, due to the complexity of cell-surface proteins, the labor-intensive workflow, and the limit of clinical samples, comprehensive characterization of the surfaceome remains extraordinarily challenging, especially in clinical studies. Developing and optimizing surfaceome enrichment methods and utilizing automated sample preparation workflow can expand the applications of surfaceome analysis and deepen our understanding of the functions of cell-surface proteins.
Keywords: Biomarker discovery; MS-based proteomics; cell-surface proteins; enrichment methods; protein dynamics; protein glycosylation; protein interactions.
The cell surface contains many important proteins such as receptors and transporters. These proteins are responsible for cells to communicate with each other, take nutrients from outside, and interact with their surroundings. Aberrant changes in surface protein expression, modifications, and interactions with other molecules directly result in various diseases, including infections, immune disorders, and cancer. Currently, mass spectrometry (MS)-based proteomics is very powerful to study proteins on a large scale, and there has been a strong interest in employing MS to investigate cell-surface proteins. In this review, we discuss different methods combining mass spectrometry with other approaches to systematically characterize protein abundance, dynamics, modification, and interaction on the cell surface. These methods help uncover protein functions and specific cell-surface proteins related to human diseases. A better understanding of the functions and properties of cell-surface proteins can facilitate the discovery of surface proteins as effective biomarkers for disease early detection and the identification of drug targets for disease treatment.