TY  - JOUR
AU  - Bianchi, Federico
AU  - Comez, Lucia
AU  - Biehl, Ralf
AU  - D’Amico, Francesco
AU  - Gessini, Alessandro
AU  - Longo, Marialucia
AU  - Masciovecchio, Claudio
AU  - Petrillo, Caterina
AU  - Radulescu, Aurel
AU  - Rossi, Barbara
AU  - Sacchetti, Francesco
AU  - Sebastiani, Federico
AU  - Violini, Nicolo
AU  - Paciaroni, Alessandro
TI  - Structure of human telomere G-quadruplex in the presence of a model drug along the thermal unfolding pathway
JO  - Nucleic acids research
VL  - 46
IS  - 22
SN  - 0301-5610
CY  - Oxford
PB  - Oxford Univ. Press
M1  - FZJ-2019-00049
SP  - 11927 - 11938
PY  - 2018
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30407585
UR  - <Go to ISI:>//WOS:000456714000026
DO  - DOI:10.1093/nar/gky1092
UR  - https://juser.fz-juelich.de/record/859105
ER  -