TY - JOUR
T1 - Structure of the intramolecular human telomeric G-quadruplex in potassium solution
T2 - A novel adenine triple formation
AU - Dai, Jixun
AU - Punchihewa, Chandanamali
AU - Ambrus, Attila
AU - Chen, Ding
AU - Jones, Roger A.
AU - Yang, Danzhou
N1 - Funding Information:
We thank Dr. Laurence Hurley for insightful comments and suggestions. We thank Dr. John Trent at the University of Louisville for performing the HYDROPRO calculations on our structures. We thank Dr. Megan Carver for technical help and proofreading the manuscript. This research was supported by the National Institutes of Health (1K01CA83886 and 1S10 RR16659). The Open Access publication charges were waived by Oxford University Press.
PY - 2007/4
Y1 - 2007/4
N2 - 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.
AB - 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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U2 - 10.1093/nar/gkm009
DO - 10.1093/nar/gkm009
M3 - Article
C2 - 17395643
AN - SCOPUS:34249846802
VL - 35
SP - 2440
EP - 2450
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 7
ER -