Staphylococcus aureus is an anaerobic facultative microorganism that features the NreABC system for nitrate respiration. NreB is the sensor histidine kinase that phosphorylates the response regulator NreC to stimulate the expression of target genes. NreA is a nitrate sensor which dissociates from NreB in the present of nitrate and relieves its inhibition on NreB. However, the molecular basis of how NreA regulate NreB remains unknown. In this study, we determined the crystal structures of nitrate-bound NreA from S. aureus (SaNreA/NO3-) and its apoNreA-like mutant SaNreAY(94A) in complex with ethanediol (SaNreA(Y94A)/EDO). Structural comparison reveals that the C-terminal loop in SaNreA/NO3- rearranges to an alpha-helix (alpha 7) in SaNreA(Y94A)/EDO, which converts an acidic pocket on the surface to a positively charged region. This conformational change of SaNreA C-terminus might play a role in SaNreB binding.