Nucleic Acids Research, Vol 24, Issue 13 2488-2497, Copyright © 1996 by Oxford University Press
AJ Doherty, LC Serpell and CP Ponting
One, two or four copies of the 'helix-hairpin-helix' (HhH) DNA-binding
motif are predicted to occur in 14 homologous families of proteins. The
predicted DNA-binding function of this motif is shown to be consistent with
the crystallographic structure of rat polymerase beta, complexed with DNA
template-primer [Pelletier, H., Sawaya, M.R., Kumar, A., Wilson, S.H. and
Kraut, J. (1994) Science 264, 1891-1903] and with biochemical data. Five
crystal structures of predicted HhH motifs are currently known: two from
rat pol beta and one each in endonuclease III, AlkA and the 5' nuclease
domain of Taq pol I. These motifs are more structurally similar to each
other than to any other structure in current databases, including
helix-turn-helix motifs. The clustering of the five HhH structures
separately from other bi-helical structures in searches indicates that all
members of the 14 families of proteins described herein possess similar HhH
structures. By analogy with the rat pol beta structure, it is suggested
that each of these HhH motifs bind DNA in a non-sequence-specific manner,
via the formation of hydrogen bonds between protein backbone nitrogens and
DNA phosphate groups. This type of interaction contrasts with the
sequence-specific interactions of other motifs, including helix-turn-helix
structures. Additional evidence is provided that alphaherpesvirus virion
host shutoff proteins are members of the polymerase I 5'-nuclease and FEN1-
like endonuclease gene family, and that a novel HhH-containing DNA- binding
domain occurs in the kinesin-like molecule nod, and in other proteins such
as cnjB, emb-5 and SPT6.
ARTICLES
The helix-hairpin-helix DNA-binding motif: a structural basis for non- sequence-specific recognition of DNA
Laboratory of Molecular Biophysics, University of Oxford, UK.
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G. I. Belova, R. Prasad, S. A. Kozyavkin, J. A. Lake, S. H. Wilson, and A. I. Slesarev A type IB topoisomerase with DNA repair activities PNAS, May 22, 2001; 98(11): 6015 - 6020. [Abstract] [Full Text] [PDF]
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M. Ariyoshi, T. Nishino, H. Iwasaki, H. Shinagawa, and K. Morikawa Crystal structure of the Holliday junction DNA in complex with a single RuvA tetramer PNAS, July 18, 2000; 97(15): 8257 - 8262. [Abstract] [Full Text] [PDF]
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