The structural ensemble of a Holliday junction determined by X-ray scattering interference.


Journal

Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011

Informations de publication

Date de publication:
20 08 2020
Historique:
accepted: 26 06 2020
revised: 31 05 2020
received: 13 10 2019
pubmed: 1 7 2020
medline: 11 11 2020
entrez: 30 6 2020
Statut: ppublish

Résumé

The DNA four-way (Holliday) junction is the central intermediate of genetic recombination, yet key aspects of its conformational and thermodynamic properties remain unclear. While multiple experimental approaches have been used to characterize the canonical X-shape conformers under specific ionic conditions, the complete conformational ensemble of this motif, especially at low ionic conditions, remains largely undetermined. In line with previous studies, our single-molecule Förster resonance energy transfer (smFRET) measurements of junction dynamics revealed transitions between two states under high salt conditions, but smFRET could not determine whether there are fast and unresolvable transitions between distinct conformations or a broad ensemble of related states under low and intermediate salt conditions. We therefore used an emerging technique, X-ray scattering interferometry (XSI), to directly probe the conformational ensemble of the Holliday junction across a wide range of ionic conditions. Our results demonstrated that the four-way junction adopts an out-of-plane geometry under low ionic conditions and revealed a conformational state at intermediate ionic conditions previously undetected by other methods. Our results provide critical information to build toward a full description of the conformational landscape of the Holliday junction and underscore the utility of XSI for probing conformational ensembles under a wide range of solution conditions.

Identifiants

pubmed: 32597986
pii: 5864709
doi: 10.1093/nar/gkaa509
pmc: PMC7641307
doi:

Substances chimiques

DNA, Cruciform 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

8090-8098

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM132899
Pays : United States

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

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Auteurs

Thomas Zettl (T)

Department of Physics, Nanosystems Initiative Munich, and Center for Nanoscience, LMU Munich, 80799 Munich, Germany.
Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.

Xuesong Shi (X)

Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.

Steve Bonilla (S)

Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.

Steffen M Sedlak (SM)

Department of Physics, Nanosystems Initiative Munich, and Center for Nanoscience, LMU Munich, 80799 Munich, Germany.

Jan Lipfert (J)

Department of Physics, Nanosystems Initiative Munich, and Center for Nanoscience, LMU Munich, 80799 Munich, Germany.

Daniel Herschlag (D)

Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
Stanford ChEM-H, Stanford University, Stanford, CA 94305, USA.

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Classifications MeSH