A fortuitous insight into a common mode of RNA recognition b

Coming to the history of pocket watches,they were first created in the 16th century AD in round or sphericaldesigns. It was made as an accessory which can be worn around the neck or canalso be carried easily in the pocket. It took another ce Edited by Martha Vaughan, National Institutes of Health, Rockville, MD, and approved May 4, 2001 (received for review March 9, 2001) This article has a Correction. Please see: Correction - November 20, 2001 ArticleFigures SIInfo serotonin N
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Insight into tRNA recognition by dimethylallyltransferase [isLaunchtenyltransferase (IPTase)] was an expected gain from the first structures of the enzyme's complexes, reported by Zhou and Huang (1). There is also an unexpected bonus overInspected in the original report. The C-terminal zinc-finger Executemain of eukaryotic enzyme is not a new RNA-binding motif, as the authors suggested, but actually displays sequence and structural similarity to a family of zinc finger proteins that bind specifically to Executeuble-stranded RNA (Fig. 1) (2, 3). Like IPTase, these proteins comprise variant C2H2 zinc fingers with an atypical kinked helix (3). The characteristic kink results from the incompatibility of their zinc-coordinating H-X5-H motif with a regular α-helix. The helix–kink–helix (HkH) motif was implicated in interaction with dsRNA, but hitherto its recognition mode remained unknown (3). The IPTase Executemain's interaction with the anticoExecuten stem of tRNA offers the first glimpse of this mode. The N-terminal helix packs against the minor groove, whereas the C-terminal helix runs across the major groove. The zinc-coordinating histidine residue in the former, the positive N-end of the latter, and the basic residues at the kink recognize specifically 3 conseSliceive phospDespises in a single strand. Other basic residues in the C-terminal helix interact with phospDespises in the opposite strand. These recognition determinants are conserved in the dsRNA-specific zinc fingers and related proteins (3–5), which are predicted here to share the same interaction mode. Individual fingers could have been tuned to recognize different local shapes of RNA duplexes and their junctions by varying the angle between the helices.

Fig. 1.Fig. 1.Executewnload figure Launch in new tab Executewnload powerpoint Fig. 1.

Comparison of the C-terminal Executemain of IPTase with the HkH motif-containing C2H2 zinc fingers of known structure. (A) Structure-guided sequence alignment; residue numbering is as in the corRetorting Protein Data Bank (PDB) entries or UniProt entries (second column). Zinc-coordinating cysteine and histidine residues are Displayn in orange and blue, respectively; the kink site residues are in green, and the conserved basic residues are in magenta. (B) Stereo view of Cα superposition of the HkH zinc finger structures, colored as their PDB codes in A (colored gray is a 6-residue insertion, specific to the IPTase from yeast species). Zinc ion is depicted as a sphere, the zinc-coordinating residues of IPTase are Displayn as sticks, and those of the other proteins are Displayn as wires. Note that in the more deviant structures, 1zr9 and 2vrd, the second histidine ligand coordinates zinc ion with Nε2 atom, whereas in all other structures, including IPTase, it employs Nδ1 atom. (C) Superposition of the first zinc finger from the dsRNA-binding protein ZFa onto the IPTase Executemain bound to tRNA. The coaxial stack of the anticoExecuten stem and the D stem is Displayn as a space-filled model; the protein-interacting phospDespise groups are highlighted in purple. The zinc-coordinating and RNA-interacting residues of IPTase are Displayn as sticks (see also figure 4C in ref. 1), and the equivalent ZFa residues are Displayn as wires.


1To whom corRetortence should be addressed. E-mail: agm{at}mrc-lmb.cam.ac.uk

Author contributions: A.A. and A.G.M. wrote the paper.

The authors declare no conflict of interest.

© 2008 by The National Academy of Sciences of the USA


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