Proteins in all biological systems are highly organized in three-dimensional space, forming membrane-enclosed or membraneless compartments, signaling pathways, dynamic assemblies, and stable complexes. Many of these structures are only viable in their native environment, making them recalcitrant to traditional biochemical characterization. Proteome-wide cross-linking mass spectrometry offers the opportunity to capture the interactions and spatial arrangement of proteins without having to extract them from their complex biological system.
Over the years, we’ve advanced cross-linking mass spectrometry by developing experimental methods and software tools and generated tens of thousands of protein-protein interactions (PPIs) from various biological systems, such as mitochondria, synapses, cells and virus particles. These data reveal numerous aspects of living systems - for example protein subcellular localizations, interactions, and architectures of suprabiomolecular machineries. Furthermore, these data offer unprecedented opportunities to profile interactome changes between tissues and disease states, providing invaluable training data for AI-based methods to identify PPI-mediating motifs, inform new protein/antibody designs and screen for drug targets.
