Abstract
Signal transduction by histidine kinases (HKs) is nearly ubiquitous in bacterial species. HKs can either sense ligands directly or indirectly via a cognate solute-binding protein (SBP). The molecular basis for SBP-dependent signal reception, however, remains poorly understood in most cases. CBP and ChiS are the SBP-HK pair that activate the chitin utilization program of Vibrio cholerae. Here, we elucidate the molecular basis for allosteric regulation of CBP-ChiS by generating structural models of this complex in the unliganded and liganded states, which we support with extensive genetic, biochemical, and cell biological analysis. Our results reveal that ligand-binding induces a large conformational interface switch that is distinct from previously described SBP-HKs. Structural modeling suggests that similar interface switches may also regulate other uncharacterized SBP-HKs. Together, these results extend our understanding of signal transduction in bacterial species and highlight an approach for uncovering the molecular basis of allostery in protein complexes.