Mapping functional regions of essential bacterial proteins with dominant-negative protein fragments.

ABSTRACT: Massively parallel measurements of dominant-negative inhibition by protein fragments have been used to map protein interaction sites and discover peptide inhibitors. However, the underlying principles governing fragment-based inhibition have thus far remained unclear. Here, we adapted a high-throughput inhibitory fragment assay for use in Escherichia coli, applying it to a set of 10 essential proteins. This approach yielded single amino acid resolution maps of inhibitory activity, with peaks localized to functionally important interaction sites, including oligomerization interfaces and folding contacts. Leveraging these data, we performed a systematic analysis to uncover principles of fragment-based inhibition. We determined a robust negative correlation between susceptibility to in

SUBMITTER: Savinov A 

PROVIDER: S-EPMC9245647 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature