Nucleic Acids Research Advance Access originally published online on March 25, 2009
Nucleic Acids Research 2009 37(10):3310-3320; doi:10.1093/nar/gkp181
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Nucleic Acids Research, 2009, Vol. 37, No. 10 3310-3320
© 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 |
Direct experimental evidence for quadruplex–quadruplex interaction within the human ILPR
Department of Chemistry, School of Biomedical Sciences, Kent State University, Kent, OH 44242, USA
*To whom correspondence should be addressed. Tel: +1 330 672 9380; Fax: +1 330 672 3816; Email: hmao{at}kent.edu
Correspondence may also be addressed to Soumitra Basu. Tel: +1 330 672 3906; Fax: +1 330 672 3816; Email: sbasu{at}kent.edu
Received January 22, 2009. Revised March 4, 2009. Accepted March 5, 2009.
Here we report the analysis of dual G-quadruplexes formed in the four repeats of the consensus sequence from the insulin-linked polymorphic region (ACAGGGGTGTGGGG; ILPRn=4). Mobilities of ILPRn=4 in nondenaturing gel and circular dichroism (CD) studies confirmed the formation of two intramolecular G-quadruplexes in the sequence. Both CD and single molecule studies using optical tweezers showed that the two quadruplexes in the ILPRn=4 most likely adopt a hybrid G-quadruplex structure that was entirely different from the mixture of parallel and antiparallel conformers previously observed in the single G-quadruplex forming sequence (ILPRn=2). These results indicate that the structural knowledge of a single G-quadruplex cannot be automatically extrapolated to predict the conformation of multiple quadruplexes in tandem. Furthermore, mechanical pulling of the ILPRn=4 at the single molecule level suggests that the two quadruplexes are unfolded cooperatively, perhaps due to a quadruplex–quadruplex interaction (QQI) between them. Additional evidence for the QQI was provided by DMS footprinting on the ILPRn=4 that identified specific guanines only protected in the presence of a neighboring G-quadruplex. There have been very few experimental reports on multiple G-quadruplex-forming sequences and this report provides direct experimental evidence for the existence of a QQI between two contiguous G-quadruplexes in the ILPR.
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