Structure of the human telomere in K+ solution: a stable basket-type G-quadruplex with only two G-tetrad layers.
Previously, it has been reported that human telomeric DNA sequences could adopt in different experimental conditions four different intramolecular G-quadruplexes each involving three G-tetrad layers, namely, Na(+) solution antiparallel-stranded basket form, K(+) crystal parallel-stranded propeller form, K(+) solution (3 + 1) Form 1, and K(+) solution (3 + 1) Form 2. Here we present a new intramolecular G-quadruplex adopted by a four-repeat human telomeric sequence in K(+) solution (Form 3). This structure is a basket-type G-quadruplex with only two G-tetrad layers: loops are successively edgewise, diagonal, and edgewise; glycosidic conformations of guanines are syn x syn x anti x anti around each tetrad. Each strand of the core has both a parallel and an antiparallel adjacent strands; there are one narrow, one wide, and two medium grooves. Despite the presence of only two G-tetrads in the core, this structure is more stable than the three-G-tetrad intramolecular G-quadruplexes previously observed for human telomeric sequences in K(+) solution. Detailed structural elucidation of Form 3 revealed extensive base pairing and stacking in the loops capping both ends of the G-tetrad core, which might explain the high stability of the structure. This novel structure highlights the conformational heterogeneity of human telomeric DNA. It establishes a new folding principle for G-quadruplexes and suggests new loop sequences and structures for targeting in human telomeric DNA.
Lim
Kah Wai
KW
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
Amrane
Samir
S
Bouaziz
Serge
S
Xu
Weixin
W
Mu
Yuguang
Y
Patel
Dinshaw J
DJ
Luu
Kim Ngoc
KN
Phan
Anh Tuân
AT
D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D011188:Potassium / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D016615:Telomere / Q000737:chemistry*; D013696:Temperature
D006147:Guanine; D004247:DNA; D011188:Potassium