Crystal structure of the archaeal heat shock regulator from Pyrococcus furiosus: a molecular chimera representing eukaryal and bacterial features.
We report here the crystal structure of a protein from Pyrococcus furiosus (Phr) that represents the first characterized heat shock transcription factor in archaea. Phr specifically represses the expression of heat shock genes at physiological temperature in vitro and in vivo but is released from the promoters upon heat shock response. Structure analysis revealed a stable homodimer, each subunit consisting of an N-terminal winged helix DNA-binding domain (wH-DBD) and a C-terminal antiparallel coiled coil helical domain. The overall structure shows as a molecular chimera with significant folding similarity of its DBD to the bacterial SmtB/ArsR family, while its C-terminal part was found to be a remote homologue of the eukaryotic BAG domain. The dimeric protein recognizes a palindromic DNA sequence. Molecular docking and mutational analyses suggested a novel binding mode in which the major specific contacts occur at the minor groove interacting with the strongly basic wing containing a cluster of three arginine residues.
Liu
Wei
W
Karolinska Institutet NOVUM, Center for Structural Biochemistry, 141 57 Huddinge, Sweden. wei.liu@biosci.ki.se
Vierke
Gudrun
G
Wenke
Ann-Kathrin
AK
Thomm
Michael
M
Ladenstein
Rudolf
R
D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D018360:Crystallography, X-Ray; D019281:Dimerization; D019143:Evolution, Molecular; D019848:Gene Expression Regulation, Archaeal; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017354:Point Mutation; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020027:Pyrococcus furiosus / Q000737:chemistry* / Q000235:genetics; D016415:Sequence Alignment; D055672:Static Electricity
D019843:Archaeal Proteins; D006360:Heat-Shock Proteins; D021122:Protein Subunits