Nucleic Acids Research Advance Access originally published online on March 24, 2009
Nucleic Acids Research 2009 37(10):3264-3275; doi:10.1093/nar/gkp191
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Nucleic Acids Research, 2009, Vol. 37, No. 10 3264-3275
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Structural Biology |
Self-association of short DNA loops through minor groove C:G:G:C tetrads
1Departament de Química Orgànica and IBUB, Universitat de Barcelona, C/. Martí i Franquès 1-11, 08028 Barcelona 2Instituto de Química Física ‘Rocasolano’, CSIC, C/. Serrano 119, 28006 Madrid, Spain
*To whom correspondence should be addressed. Tel: +34 915619400; Fax: +34 915642431; Email: cgonzalez{at}iqfr.csic.es
Correspondence may also be addressed to Enrique Pedroso. Tel: +34 934034824; Fax: +34 933397878; Email: epedroso{at}ub.edu
Received January 22, 2009. Revised March 6, 2009. Accepted March 9, 2009.
In addition to the better known guanine-quadruplex, four-stranded nucleic acid structures can be formed by tetrads resulting from the association of Watson–Crick base pairs. When such association occurs through the minor groove side of the base pairs, the resulting structure presents distinctive features, clearly different from quadruplex structures containing planar G-tetrads. Although we have found this unusual DNA motif in a number of cyclic oligonucleotides, this is the first time that this DNA motif is found in linear oligonucleotides in solution, demonstrating that cyclization is not required to stabilize minor groove tetrads in solution. In this article, we have determined the solution structure of two linear octamers of sequence d(TGCTTCGT) and d(TCGTTGCT), and their cyclic analogue d<pCGCTCCGT>, utilizing 2D NMR spectroscopy and restrained molecular dynamics. These three molecules self-associate forming symmetric dimers stabilized by a novel kind of minor groove C:G:G:C tetrad, in which the pattern of hydrogen bonds differs from previously reported ones. We hypothesize that these quadruplex structures can be formed by many different DNA sequences, but its observation in linear oligonucleotides is usually hampered by competing Watson–Crick duplexes.