Cell type-independent profiling of interactions between intracellular pathogens and the human phosphoproteome

Mohler, K.; Moen, J.; Rogulina, S.; Rinehart, J.

doi:10.1101/2022.09.27.509702

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bioRxiv · 10.1101/2022.09.27.509702

Cell type-independent profiling of interactions between intracellular pathogens and the human phosphoproteome

Mohler, K.·Moen, J.·Rogulina, S.·Rinehart, J.

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Abstract

Interactions between proteins from intracellular pathogens and host proteins in an infected cell are often mediated by post-translational modifications encoded in the host proteome. Identifying protein modifications, such as phosphorylation, that dictate these interactions remains a defining challenge in unraveling the molecular mechanisms of pathogenesis. We have developed a platform in engineered bacteria that displays over 110,000 phosphorylated human proteins coupled to a fluorescent reporter system capable of identifying the host-pathogen interactome of phosphoproteins (H-PIP). This resource broadly enables cell-type independent interrogation and discovery of proteins from intracellular pathogens capable of binding phosphorylated human proteins. As an example of the H-PIP platform, we generated a unique, high-resolution SARS-CoV-2 interaction network which expanded our knowledge of viral protein function and identified understudied areas of host pathology.

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Mohler, K., Moen, J., Rogulina, S., Rinehart, J.. 2022-09-28. Cell type-independent profiling of interactions between intracellular pathogens and the human phosphoproteome. https://doi.org/10.1101/2022.09.27.509702

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