A novel chair-type G-quadruplex formed by a Bombyx mori telomeric sequence
نویسندگان
چکیده
Recently, the human telomeric d[TAGGG(TTAGGG)(3)] sequence has been shown to form in K(+) solution an intramolecular (3+1) G-quadruplex structure, whose G-tetrad core contains three strands oriented in one direction and the fourth in the opposite direction. Here we present a study on the structure of the Bombyx mori telomeric d[TAGG(TTAGG)(3)] sequence, which differs from the human counterpart only by one G deletion in each repeat. We found that this sequence adopted multiple G-quadruplex structures in K(+) solution. We have favored a major G-quadruplex form by a judicious U-for-T substitution in the sequence and determined the folding topology of this form. We showed by NMR that this was a new chair-type intramolecular G-quadruplex which involved a two-layer antiparallel G-tetrad core and three edgewise loops. Our result highlights the effect of G-tract length on the folding topology of G-quadruplexes, but also poses the question of whether a similar chair-type G-quadruplex fold exists in the human telomeric sequences.
منابع مشابه
Human telomeric sequence forms a hybrid-type intramolecular G-quadruplex structure with mixed parallel/antiparallel strands in potassium solution
Human telomeric DNA consists of tandem repeats of the sequence d(TTAGGG). The formation and stabilization of DNA G-quadruplexes in the human telomeric sequence have been shown to inhibit the activity of telomerase, thus the telomeric DNA G-quadruplex has been considered as an attractive target for cancer therapeutic intervention. However, knowledge of the intact human telomeric G-quadruplex str...
متن کاملStructure of a two-G-tetrad intramolecular G-quadruplex formed by a variant human telomeric sequence in K+ solution: insights into the interconversion of human telomeric G-quadruplex structures
Human telomeric DNA G-quadruplex has been considered as an attractive target for cancer therapeutic intervention. The telomeric sequence shows intrinsic structure polymorphism. Here we report a novel intramolecular G-quadruplex structure formed by a variant human telomeric sequence in K(+) solution. This sequence forms a basket-type intramolecular G-quadruplex with only two G-tetrads but multip...
متن کاملStructure of the Hybrid-2 type intramolecular human telomeric G-quadruplex in K+ solution: insights into structure polymorphism of the human telomeric sequence
Formation of the G-quadruplex in the human telomeric sequence can inhibit the activity of telomerase, thus the intramolecular telomeric G-quadruplexes have been considered as an attractive anticancer target. Information of intramolecular telomeric G-quadruplex structures formed under physiological conditions is important for structure-based drug design. Here, we report the first structure of th...
متن کاملStructure of the human telomere in Na+ solution: an antiparallel (2+2) G-quadruplex scaffold reveals additional diversity
Single-stranded DNA overhangs at the ends of human telomeric repeats are capable of adopting four-stranded G-quadruplex structures, which could serve as potential anticancer targets. Out of the five reported intramolecular human telomeric G-quadruplex structures, four were formed in the presence of K(+) ions and only one in the presence of Na(+) ions, leading often to a perception that this str...
متن کاملStructural polymorphism of intramolecular quadruplex of human telomeric DNA: effect of cations, quadruplex-binding drugs and flanking sequences
G-quadruplex structures formed in the telomeric DNA are thought to play a role in the telomere function. Drugs that stabilize the G-quadruplexes were shown to have anticancer effects. The structures formed by the basic telomeric quadruplex-forming unit G(3)(TTAG(3))(3) were the subject of multiple studies. Here, we employ (125)I-radioprobing, a method based on analysis of the distribution of DN...
متن کامل