Structural basis of operator sites recognition and effector binding in the TetR family transcription regulator FadR.
FadR is a fatty acyl-CoA dependent transcription factor that regulates genes encoding proteins involved in fatty-acid degradation and synthesis pathways. In this study, the crystal structures of Bacillus halodurans FadR, which belong to the TetR family, have been determined in three different forms: ligand-bound, ligand-free and DNA-bound at resolutions of 1.75, 2.05 and 2.80 Å, respectively. Structural and functional data showed that B. halodurans FadR was bound to its operator site without fatty acyl-CoAs. Structural comparisons among the three different forms of B. halodurans FadR revealed that the movement of DNA binding domains toward the operator DNA was blocked upon binding of ligand molecules. These findings suggest that the TetR family FadR negatively regulates the genes involved in fatty acid metabolism by binding cooperatively to the operator DNA as a dimer of dimers.
Department of Life Science, Dongguk University-Seoul, 32, Dongguk-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10326, Republic of Korea.
Hyun Ku
HK
Yeo
Department of Life Science, Dongguk University-Seoul, 32, Dongguk-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10326, Republic of Korea.
Young Woo
YW
Park
Department of Life Science, Dongguk University-Seoul, 32, Dongguk-ro, Ilsandong-gu, Goyang, Gyeonggi-do 10326, Republic of Korea.
Jae Young
JY
Lee
D001407:Bacillus / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D004269:DNA, Bacterial / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009875:Operator Regions, Genetic; D011485:Protein Binding; D011487:Protein Conformation; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism
D001426:Bacterial Proteins; D004269:DNA, Bacterial; C057119:FadR protein, Bacteria; D012097:Repressor Proteins