Integrated mass spectrometry strategy for functional protein complex discovery and structural characterization

The discovery of functional protein complex and the interro-gation of the complex structure-function relationship (SFR) play crucial roles in the understanding and intervention of biological processes. Affinity purification-mass spectrometry (AP-MS) has been proved as a powerful tool in the discovery of protein complexes. However, validation of these novel protein complexes as well as elucidation of their molecular interaction mechanisms are still challenging. Recently, native top-down MS (nTDMS) is rapidly developed for the structural analysis of protein complexes. In this review, we discuss the integration of AP-MS and nTDMS in the discovery and structural charac-terization of functional protein complexes. Further, we think the emerging artificial intelligence (AI)-based protein structure prediction is highly complementary to nTDMS and can pro -mote each other. We expect the hybridization of integrated structural MS with AI prediction to be a powerful workflow in the discovery and SFR investigation of functional protein complexes.

Automated summary

The discovery and understanding of functional protein complexes are crucial for the intervention in biological processes. The combination of affinity purification-mass spectrometry (AP-MS) and native top-down MS (nTDMS) has been developed to discover and analyze the structure of protein complexes. The integration of artificial intelligence (AI) with nTDMS can further enhance the investigation of functional protein complexes.