%0 Journal Article
%A Bianchi, Federico
%A Comez, Lucia
%A Biehl, Ralf
%A D’Amico, Francesco
%A Gessini, Alessandro
%A Longo, Marialucia
%A Masciovecchio, Claudio
%A Petrillo, Caterina
%A Radulescu, Aurel
%A Rossi, Barbara
%A Sacchetti, Francesco
%A Sebastiani, Federico
%A Violini, Nicolo
%A Paciaroni, Alessandro
%T Structure of human telomere G-quadruplex in the presence of a model drug along the thermal unfolding pathway
%J Nucleic acids research
%V 46
%N 22
%@ 0301-5610
%C Oxford
%I Oxford Univ. Press
%M FZJ-2019-00049
%P 11927 - 11938
%D 2018
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:30407585
%U <Go to ISI:>//WOS:000456714000026
%R 10.1093/nar/gky1092
%U https://juser.fz-juelich.de/record/859105