Di-HAMP domains of a cytoplasmic chemoreceptor modulate nucleoid array formation and downstream signalling

Abstract

In bacterial chemosensing, environmental cues are typically sensed by bacterial transmembrane receptors known as methyl accepting chemotaxis proteins (MCPs). MCPs form highly organized arrays using the bacterial membrane as a scaffold, which amplify the signals and transduce them into a cellular response. The FrzCD cytoplasmic receptor from Myxococcus xanthus is unique due to its ability to bind DNA and use the nucleoid as a scaffold to form arrays. In this study, we identified two HAMP (histidine kinase, adenylyl cyclase, MCP and phosphatase) domains located between the DNA binding and signaling domains of FrzCD. In vitro experiments demonstrate that these HAMP domains restrict FrzCD to a dimeric form in solution and modulate FrzCDs affinity for DNA, whereas the signaling domain stabilizes higher-order oligomeric assemblies upon DNA binding. Through fluorescence microscopy and analyses on Myxococcus social behavior, we demonstrate that the impact of FrzCD HAMP domains on DNA binding and oligomerization significantly influences group motility and development. Our results suggest that HAMP domains might have roles not only in signal transduction but also in the plasticity of chemosensory arrays. These observations illustrate mechanisms of regulation of a DNA-bound cytoplasmic array formed by a diffusible MCP. Significance StatementOur study identifies the presence of tandem HAMP domains in a cytoplasmic chemoreceptor, FrzCD, from Myxococcus xanthus, and highlights their role in dynamic receptor oligomerization on a DNA scaffold. By controlling receptor oligomerization and subsequently the array formation on the nucleoid, the tandem HAMP domains impart plasticity to the receptor arrays. Such plasticity governs cellular responses to external signals and dictate bacterial social behavior in group motility and multicellular structure formation.