Nucleic Acids Research Advance Access originally published online on March 29, 2007
Nucleic Acids Research 2007 35(7):2440-2450; doi:10.1093/nar/gkm009
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Nucleic Acids Research, 2007, Vol. 35, No. 7 2440-2450
© 2007 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 |
Structure of the intramolecular human telomeric G-quadruplex in potassium solution: a novel adenine triple formation
1College of Pharmacy, The University of Arizona, 1703 E. Mabel St, Tucson, AZ 85721, USA, 2Department of Chemistry and Chemical Biology, Rutgers University, 610 Taylor Road, Piscataway, NJ 08854, USA, 3Arizona Cancer Center, 1515 N. Campbell Avenue, Tucson, AZ 85724, USA and 4BIO5 Institute, The University of Arizona, 1140 E. South Campus Dr, Tucson, AZ 85721, USA
*To whom correspondence should be addressed. Tel: +1 520 626 5969; Fax: +1 520 626 6988; Email: yangd{at}pharmacy.arizona.edu
Received September 8, 2006. Revised December 21, 2006. Accepted December 27, 2006.
We report the NMR solution structure of the intramolecular G-quadruplex formed in human telomeric DNA in K+. The hybrid-type telomeric G-quadruplex consists of three G-tetrads linked with mixed parallel–antiparallel G-strands, with the bottom two G-tetrads having the same G-arrangement (anti:anti:syn:anti) and the top G-tetrad having the reversed G-arrangement (syn:syn:anti:syn). The three TTA loop segments adopt different conformations, with the first TTA assuming a double-chain-reversal loop conformation, and the second and third TTA assuming lateral loop conformations. The NMR structure is very well defined, including the three TTA loops and the two flanking sequences at 5'- and 3'-ends. Our study indicates that the three loop regions interact with the core G-tetrads in a specific way that defines and stabilizes the unique human telomeric G-quadruplex structure in K+. Significantly, a novel adenine triple platform is formed with three naturally occurring adenine residues, A21, A3 and A9, capping the top tetrad of the hybrid-type telomeric G-quadruplex. This adenine triple is likely to play an important role in the formation of a stable human telomeric G-quadruplex structure in K+. The unique human telomeric G-quadruplex structure formed in K+ suggests that it can be specifically targeted for anticancer drug design.
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