A novel mechanism of osmosensing, a salt-dependent protein-nucleic acid interaction in the cyanobacterium Synechocystis Species PCC 6803.

The de novo synthesis of compatible solutes is an essential part of the cellular osmotic stress response. Upon an osmotic challenge, it is regulated by the immediate biochemical activation of preformed enzymes and by activation of gene expression. Whereas the transcriptional response has been investigated intensively, the mechanisms by which enzymes are activated in osmotic stress situations are still elusive. Here, we address this topic for the moderately halotolerant cyanobacterium Synechocystis sp. PCC 6803, which synthesizes glucosylglycerol as a compatible solute. The key enzyme of the glucosylglycerol pathway (GgpS) is inhibited by nucleic acids in a sequence- and length-independent manner. The protein binds DNA, RNA, and heparin via a salt-dependent electrostatic interaction with the negatively charged backbone of the polyanions. Mechanistically, DNA binding to the enzyme causes noncompetitive inhibition of GgpS activity. The interaction of the enzyme and nucleic acids under in vivo conditions is indicated by the co-purification of both after cross-linking in Synechocystis cells. We propose a novel mechanism of activity regulation by the nonspecific salt-dependent binding of an enzyme to nucleic acids.