[S1-3] ヘム応答性センサータンパク質による溶血性細菌の生存の構造的機序
Hemes (iron-porphyrins) are essential elements in all organisms, but heme homeostasis should be regulated strictly due to the cytotoxicity of free heme molecules. Hemolytic bacteria acquire the heme from red-blood cells in hosts for growth and infection. To avoid its cytotoxicity, the heme-responsive sensor protein regulates expression of the heme efflux system as a transcriptional factor in response to the heme concentration in bacterial cells. Structure and function of a heme-responsive sensor protein PefR from β-hemolytic bacterium Streptococcus agalactiae had studied with crystallographic, spectroscopic and biochemical methods to elucidate its heme-dependent regulatory mechanisms. The unique heme coordination causes formation of a hydrophobic heme pocket and the conformational change of the DNA-binding domain. It triggers to dissociate PefR from the target DNA for depression of the genes encoding the heme efflux system. Moreover, the heme-bound PefR forms a stable complex with carbon monoxide, a by-product of heme degradation. These results provide a new concept for the development of antimicrobial agents.