Structural Modularity of Biomolecules Elucidated by Proteome Imaging

Structural modularity in tertiary or quaternary order provides us the descriptors to observe the event-driven conformations of complex macromolecules in cells. Conformational proteomics enables multimodal imaging, so as to correlate imaging across a range of instruments, to illustrate the structural events across the modality of gross morphology and fine molecular feature in order to conceptualize crucial biological processes. Integrated methods and tools are implemented to analyze how the weak-force associations are transformed based on the interactions of the involved subunits. In this presentation, the multivalence of an oral DNA vaccine will be exemplified as platform technology for a nanotargeting system, whereas the protein domains are to be emphasized as modular units in directing the pathway of self-organizations for cargo packaging. Similarly, the essence of the domain/subunit interactions will be demonstrated by an HIV immunoge protein, as its tertiary modular units direct the entire quaternary organizations, engaging defined metastable conformations in discrete states to induce broader breath of immunity. Statistical advancement and heterogeneity sorting of the acquired microscopy data have played the key role in characterizing the metastable intermediates, and can now provide the essential framework to comprehend the overall function of the consequent macromolecules through evolution or engineering.