Crystal structure of Bacillus anthracis ThiI, a tRNA-modifying enzyme containing the predicted RNA-binding THUMP domain.
ThiI is an enzyme responsible for the formation of the modified base S(4)U (4-thiouridine) found at position 8 in some prokaryotic tRNAs. This base acts as a sensitive trigger for the response mechanism to UV exposure, providing protection against its damaging effects. We present the crystal structure of Bacillus anthracis ThiI in complex with AMP, revealing an extended tripartite architecture in which an N-terminal ferredoxin-like domain (NFLD) connects the C-terminal catalytic PP-loop pyrophosphatase domain with a THUMP domain, an ancient predicted RNA-binding domain that is widespread in all kingdoms of life. We describe the structure of the THUMP domain, which appears to be unrelated to RNA-binding domains of known structure. Mapping the conserved residues of NFLD and the THUMP domain onto the ThiI structure suggests that these domains jointly form the tRNA-binding surface. The inaccessibility of U8 in the canonical L-shaped form of tRNA, and the existence of a glycine-rich linker joining the catalytic and RNA-binding moieties of ThiI suggest that structural changes may occur in both molecules upon binding.
Waterman
David G
DG
York Structural Biology Laboratory, University of York, Chemistry Department, York YO10 5YW, UK. waterman@ysbl.york.ac.uk
Ortiz-Lombardía
Miguel
M
Fogg
Mark J
MJ
Koonin
Eugene V
EV
Antson
Alfred A
AA
D000595:Amino Acid Sequence; D001408:Bacillus anthracis / Q000201:enzymology*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D005288:Ferredoxins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D043902:Pyrococcus horikoshii / Q000737:chemistry / Q000378:metabolism; D011755:Pyrophosphatases / Q000737:chemistry / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D013466:Sulfurtransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D005288:Ferredoxins; D012343:RNA, Transfer; D013466:Sulfurtransferases; C107110:ThiI protein, bacteria; D011755:Pyrophosphatases