Compaction of duplex nucleic acids upon native electrospray mass spectrometry

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• dc.contributor.author Porrini, Massimilianoca
• dc.contributor.author Rosu, Frédéricca
• dc.contributor.author Rabin, Clémenceca
• dc.contributor.author Darré, Leonardoca
• dc.contributor.author Gómez, Hanselca
• dc.contributor.author Orozco, Modestoca
• dc.contributor.author Gabelica, Valérieca
• dc.date.accessioned 2018-05-15T07:15:20Z
• dc.date.available 2018-05-15T07:15:20Z
• dc.date.issued 2017
• dc.description.abstract We report on the fate of nucleic acids conformation in the gas phase as sampled using native mass spectrometry coupled to ion mobility spectrometry. On the basis of several successful reports for proteins and their complexes, the technique has become popular in structural biology, and the conformation survival becomes more and more taken for granted. Surprisingly, we found that DNA and RNA duplexes, at the electrospray charge states naturally obtained from native solution conditions (≥100 mM aqueous NH4OAc), are significantly more compact in the gas phase compared to the canonical solution structures. The compaction is observed for all duplex sizes (gas-phase structures are more compact than canonical B-helices by ∼20% for 12-bp, and by up to ∼30% for 36-bp duplexes), and for DNA and RNA alike. Molecular modeling (density functional calculations on small helices, semiempirical calculations on up to 12-bp, and molecular dynamics on up to 36-bp duplexes) demonstrates that the compaction is due to phosphate group self-solvation prevailing over Coulomb repulsion. Molecular dynamics simulations starting from solution structures do not reproduce the experimental compaction. To be experimentally relevant, molecular dynamics sampling should reflect the progressive structural rearrangements occurring during desolvation. For nucleic acid duplexes, the compaction observed for low charge states results from novel phosphate-phosphate hydrogen bonds formed across both grooves at the very late stages of electrospray.
• dc.description.sponsorship This work was funded by the European Research Council (ERC DNAFOLDIMS to V.G. and ERC SimDNA to M.O.), by the Spanish BIO2015-69802-R grant to MO, and by EU COST action BM1403 (short-term scientific mission to MP). HG is a Juan de la Cierva researcher. LD is a SNI (Sistema Nacional de Investigadores; ANII, Uruguay) researcher, and MO is an ICREA-academia fellow.
• dc.format.mimetype application/pdf
• dc.identifier.citation Porrini M, Rosu F, Rabin C, Darré L, Gómez H, Orozco M et al. Compaction of Duplex Nucleic Acids upon Native Electrospray Mass Spectrometry. ACS Cent. Sci. 2017 May; 3(5): 454-461. DOI: 10.1021/acscentsci.7b00084
• dc.identifier.doi http://dx.doi.org/10.1021/acscentsci.7b00084
• dc.identifier.issn 2374-7943
• dc.identifier.uri http://hdl.handle.net/10230/34632
• dc.language.iso eng
• dc.publisher American Chemical Society (ACS)ca
• dc.relation.ispartof ACS Cent. Sci. 2017 May; 3(5): 454-461
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/616551
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/291433
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BIO2015-69802-R
• dc.rights This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Duplex nucleic acids
• dc.subject.keyword Mass spectrometry
• dc.subject.keyword Electrospray ionization
• dc.title Compaction of duplex nucleic acids upon native electrospray mass spectrometryca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion