Open Access3D Heteronuclear Magnetization Transfers for the Establishment of Secondary Structures in SARS-CoV-2-Derived RNAs
Author(s) -
Jihyun Kim,
Mihajlo Novakovic,
S. Jayanthi,
Adonis Lupulescu,
Ēriks Kupče,
J. Tassilo Grün,
Klara R. Mertinkus,
Andreas Oxenfarth,
Christian Richter,
Robbin Schnieders,
Julia WirmerBartoschek,
Harald Schwalbe,
Lucio Frydman
Publication year - 2021
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.1c01914
Subject(s) - homonuclear molecule , heteronuclear molecule , two dimensional nuclear magnetic resonance spectroscopy , chemistry , nucleic acid , heteronuclear single quantum coherence spectroscopy , rna , nuclear magnetic resonance spectroscopy , stereochemistry , molecule , biochemistry , organic chemistry , gene
Multidimensional NOESY experiments targeting correlations between exchangeable imino and amino protons provide valuable information about base pairing in nucleic acids. It has been recently shown that the sensitivity of homonuclear correlations involving RNA's labile imino protons can be significantly enhanced, by exploiting the repolarization brought about by solvent exchanges. Homonuclear correlations, however, are of limited spectral resolution, and usually incapable of tackling relatively large homopolymers with repeating structures like RNAs. This study presents a heteronuclear-resolved version of those NOESY experiments, in which magnetization transfers between the aqueous solvent and the nucleic acid protons are controlled by selecting specific chemical shift combinations of a coupled 1 H- 15 N spin pair. This selective control effectively leads to a pseudo-3D version of HSQC-NOESY, but with cross-peaks enhanced by ∼2-5× as compared with conventional 2D NOESY counterparts. The enhanced signal sensitivity as well as access to both 15 N- 1 H and 1 H- 1 H NOESY dimensions can greatly facilitate RNA assignments and secondary structure determinations, as demonstrated here with the analysis of genome fragments derived from the SARS-CoV-2 virus.