Signaling nucleotides are integral parts of signal transduction
systems allowing bacteria to cope with and rapidly respond to
changes in the environment. The Staphylococcus aureus PII-like
signal transduction protein PstA was recently identified as a
cyclic diadenylate monophosphate (c-di-AMP)-binding protein.
Here, we present the crystal structures of the apo- and c-diAMP-bound
PstA protein, which is trimeric in solution as well
as in the crystals. The structures combined with detailed bioinformatics
analysis revealed that the protein belongs to a new
family of proteins with a similar core fold but with distinct features
to classical PII proteins, which usually function in nitrogen
metabolism pathways in bacteria. The complex structure
revealed three identical c-di-AMP-binding sites per trimer with
each binding site at a monomer-monomer interface. Although
distinctly different from other cyclic-di-nucleotide-binding
sites, as the half-binding sites are not symmetrical, the complex
structure also highlighted common features for c-di-AMPbinding
sites. A comparison between the apo and complex
structures revealed a series of conformational changes that
result in the ordering of two anti-parallel !-strands that protrude
from each monomer and allowed us to propose a mechanism
on how the PstA protein functions as a signaling transduction
protein.