Computational design of dynamic receptor-peptide signaling complexes applied to chemotaxis.

ABSTRACT: Engineering protein biosensors that sensitively respond to specific biomolecules by triggering precise cellular responses is a major goal of diagnostics and synthetic cell biology. Previous biosensor designs have largely relied on binding structurally well-defined molecules. In contrast, approaches that couple the sensing of flexible compounds to intended cellular responses would greatly expand potential biosensor applications. Here, to address these challenges, we develop a computational strategy for designing signaling complexes between conformationally dynamic proteins and peptides. To demonstrate the power of the approach, we create ultrasensitive chemotactic receptor-peptide pairs capable of eliciting potent signaling responses and strong chemotaxis in primary human T cells. Unlike tr

SUBMITTER: Jefferson RE 

PROVIDER: S-EPMC10198977 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature