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| Home > Publications database > Structure of human telomere G-quadruplex in the presence of a model drug along the thermal unfolding pathway > print |
| 001 | 859105 | ||
| 005 | 20210130000200.0 | ||
| 024 | 7 | _ | |a 10.1093/nar/gky1092 |2 doi |
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| 100 | 1 | _ | |a Bianchi, Federico |0 P:(DE-HGF)0 |b 0 |
| 245 | _ | _ | |a Structure of human telomere G-quadruplex in the presence of a model drug along the thermal unfolding pathway |
| 260 | _ | _ | |a Oxford |c 2018 |b Oxford Univ. Press |
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| 520 | _ | _ | |a A multi-technique approach, combining circular dichroism spectroscopy, ultraviolet resonance Raman spectroscopy and small angle scattering techniques, has been deployed to elucidate how the structural features of the human telomeric G-quadruplex d[A(GGGTTA)3GGG] (Tel22) change upon thermal unfolding. The system is studied both in the free form and when it is bound to Actinomycin D (ActD), an anticancer ligand with remarkable conformational flexibility. We find that at room temperature binding of Tel22 with ActD involves end-stacking upon the terminal G-tetrad. Structural evidence for drug-driven dimerization of a significant fraction of the G-quadruplexes is provided. When the temperature is raised, both free and bound Tel22 undergo melting through a multi-state process. We show that in the intermediate states of Tel22 the conformational equilibrium is shifted toward the (3+1) hybrid-type, while a parallel structure is promoted in the complex. The unfolded state of the free Tel22 is consistent with a self-avoiding random-coil conformation, whereas the high-temperature state of the complex is observed to assume a quite compact form. Such an unprecedented high-temperature arrangement is caused by the persistent interaction between Tel22 and ActD, which stabilizes compact conformations even in the presence of large thermal structural fluctuations. |
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| 700 | 1 | _ | |a Comez, Lucia |0 0000-0001-5160-6844 |b 1 |e Corresponding author |
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| 773 | _ | _ | |a 10.1093/nar/gky1092 |g Vol. 46, no. 22, p. 11927 - 11938 |0 PERI:(DE-600)1472175-2 |n 22 |p 11927 - 11938 |t Nucleic acids research |v 46 |y 2018 |x 0301-5610 |
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