Early Folding Dynamics of i-Motif DNA Revealed by pH-Jump Time-Resolved X-ray Solution Scattering.

Autor: Chan AM; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.; International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, United States., Ebrahimi SB; International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, United States.; Department of Chemical and Biomolecular Engineering, Northwestern University, Evanston, Illinois 60208, United States., Samanta D; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.; International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, United States., Leshchev D; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States., Nijhawan AK; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.; International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, United States., Hsu DJ; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States., Ho MB; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States., Ramani N; International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, United States.; Department of Material Science and Engineering, Northwestern University, Evanston, Illinois 60208, United States., Kosheleva I; Center for Advanced Radiation Sources, The University of Chicago, Chicago, Illinois 60637, United States., Henning R; Center for Advanced Radiation Sources, The University of Chicago, Chicago, Illinois 60637, United States., Mirkin CA; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.; International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, United States.; Department of Chemical and Biomolecular Engineering, Northwestern University, Evanston, Illinois 60208, United States.; Department of Material Science and Engineering, Northwestern University, Evanston, Illinois 60208, United States., Kohlstedt KL; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.; International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, United States., Chen LX; Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.; International Institute for Nanotechnology, Northwestern University, Evanston, Illinois 60208, United States.; Chemical Sciences and Engineering Division, Argonne National Laboratory, Argonne 60439, Illinois, United States.
Jazyk: angličtina
Zdroj: Journal of the American Chemical Society [J Am Chem Soc] 2024 Dec 11; Vol. 146 (49), pp. 33743-33752. Date of Electronic Publication: 2024 Nov 28.
DOI: 10.1021/jacs.4c11768
Abstrakt: The i-motif is a pH-responsive cytosine-rich oligonucleotide sequence that forms, under acidic conditions, a quadruplex structure. This tunable structural switching has made the i-motif a useful platform for designing pH-responsive nanomaterials. Despite the widespread application of i-motif DNA constructs as biomolecular switches, the mechanism of i-motif folding on the atomic scale has yet to be established. We investigate the early folding structural dynamics of i-motif oligonucleotides with laser-pulse-induced pH-jump time-resolved X-ray solution scattering. Following the pH-jump, we observe that the initial random coil ensemble converts into a contracted intermediate state within 113 ns followed by further folding on the 10 ms time scale. We reveal the representative structures of these transient species, hitherto unknown, with molecular dynamics simulations and ensemble fitting. These results pave the way for understanding metastable conformations of i-motif folding and for benchmarking emerging theoretical models for simulating noncanonical nucleic acid structures.
Databáze: MEDLINE
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