Discovery and characterization of dynamic modifications of membrane receptor protein machinery

<p indent="0mm">Membrane receptor protein machinery regulates the assembly of protein complexes via dynamic post-translational modifications, enabling precise spatiotemporal control of cell phenotypes. Mass spectrometry-based proteomics has become a prevalent technique for analyzing these modifications and protein complexes. We reasoned that chemical biology tool could empower mass spectrometry-based proteomics to reveal tyrosine phosphorylation modifications and protein complexes of membrane receptor protein machinery in their native environments. By capturing and enriching interacting proteins with chemical probes, we identified ligand-receptor pairs and phosphorylation-mediated protein complexes in the tumor microenvironment and immune process. Additionally, by developing chemical biology tools in living cells, we depicted the dynamic protein complexes and phosphorylation cascades regulated by membrane receptor protein machinery under specific spatiotemporal conditions.