Mechanical unfolding of the Beet Western Yellow Virus - 1 frameshift signal

Katherine H. White, Marek Orzechowski, Dominique Fourmy, Koen Visscher

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Using mechanical unfolding by optical tweezers (OT) and steered molecular dynamics (SMD) simulations, we have demonstrated the critical role of Mg 2+ ions for the resistance of the Beet Western Yellow Virus (BWYV) pseudoknot (PK) to unfolding. The two techniques were found to be complementary, providing information at different levels of molecular scale. Findings from the OT experiments indicated a critical role of stem 1 for unfolding of the PK, which was confirmed in the SMD simulations. The unfolding pathways of wild type and mutant appeared to depend upon pH and nucleotide sequence. SMD simulations support the notion that the stability of stem 1 is critical for -1 frameshifting. The all-atom scale nature of the SMD enabled clarification of the precise role of two Mg2+ ions, Mg45 and Mg52, as identified in the BWYV X-ray crystallography structure, in -1 frameshifting. On the basis of simulations with "partially" and "fully" hydrated Mg 2+ ions, two possible mechanisms of stabilizing stem 1 are proposed. In both these cases Mg2+ ions play a critical role in stabilizing stem 1, either by directly forming a salt bridge between the strands of stem 1 or by stabilizing parallel orientation of the strands in stem 1, respectively. These findings explain the unexpected drop in frameshifting efficiency to null levels of the C8U mutant in a manner consistent with experimental observations.

Original languageEnglish (US)
Pages (from-to)9775-9782
Number of pages8
JournalJournal of the American Chemical Society
Volume133
Issue number25
DOIs
StatePublished - Jun 29 2011

Fingerprint

Luteovirus
Molecular Dynamics Simulation
Viruses
Molecular dynamics
Optical Tweezers
Ions
Optical tweezers
Computer simulation
X ray crystallography
X Ray Crystallography
Nucleotides
Salts
Atoms
yellow 1 (Rhizobium loti)
Experiments

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Mechanical unfolding of the Beet Western Yellow Virus - 1 frameshift signal. / White, Katherine H.; Orzechowski, Marek; Fourmy, Dominique; Visscher, Koen.

In: Journal of the American Chemical Society, Vol. 133, No. 25, 29.06.2011, p. 9775-9782.

Research output: Contribution to journalArticle

White, Katherine H. ; Orzechowski, Marek ; Fourmy, Dominique ; Visscher, Koen. / Mechanical unfolding of the Beet Western Yellow Virus - 1 frameshift signal. In: Journal of the American Chemical Society. 2011 ; Vol. 133, No. 25. pp. 9775-9782.
@article{2747ff43dfee45df802d2f251a4f93e5,
title = "Mechanical unfolding of the Beet Western Yellow Virus - 1 frameshift signal",
abstract = "Using mechanical unfolding by optical tweezers (OT) and steered molecular dynamics (SMD) simulations, we have demonstrated the critical role of Mg 2+ ions for the resistance of the Beet Western Yellow Virus (BWYV) pseudoknot (PK) to unfolding. The two techniques were found to be complementary, providing information at different levels of molecular scale. Findings from the OT experiments indicated a critical role of stem 1 for unfolding of the PK, which was confirmed in the SMD simulations. The unfolding pathways of wild type and mutant appeared to depend upon pH and nucleotide sequence. SMD simulations support the notion that the stability of stem 1 is critical for -1 frameshifting. The all-atom scale nature of the SMD enabled clarification of the precise role of two Mg2+ ions, Mg45 and Mg52, as identified in the BWYV X-ray crystallography structure, in -1 frameshifting. On the basis of simulations with {"}partially{"} and {"}fully{"} hydrated Mg 2+ ions, two possible mechanisms of stabilizing stem 1 are proposed. In both these cases Mg2+ ions play a critical role in stabilizing stem 1, either by directly forming a salt bridge between the strands of stem 1 or by stabilizing parallel orientation of the strands in stem 1, respectively. These findings explain the unexpected drop in frameshifting efficiency to null levels of the C8U mutant in a manner consistent with experimental observations.",
author = "White, {Katherine H.} and Marek Orzechowski and Dominique Fourmy and Koen Visscher",
year = "2011",
month = "6",
day = "29",
doi = "10.1021/ja111281f",
language = "English (US)",
volume = "133",
pages = "9775--9782",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "25",

}

TY - JOUR

T1 - Mechanical unfolding of the Beet Western Yellow Virus - 1 frameshift signal

AU - White, Katherine H.

AU - Orzechowski, Marek

AU - Fourmy, Dominique

AU - Visscher, Koen

PY - 2011/6/29

Y1 - 2011/6/29

N2 - Using mechanical unfolding by optical tweezers (OT) and steered molecular dynamics (SMD) simulations, we have demonstrated the critical role of Mg 2+ ions for the resistance of the Beet Western Yellow Virus (BWYV) pseudoknot (PK) to unfolding. The two techniques were found to be complementary, providing information at different levels of molecular scale. Findings from the OT experiments indicated a critical role of stem 1 for unfolding of the PK, which was confirmed in the SMD simulations. The unfolding pathways of wild type and mutant appeared to depend upon pH and nucleotide sequence. SMD simulations support the notion that the stability of stem 1 is critical for -1 frameshifting. The all-atom scale nature of the SMD enabled clarification of the precise role of two Mg2+ ions, Mg45 and Mg52, as identified in the BWYV X-ray crystallography structure, in -1 frameshifting. On the basis of simulations with "partially" and "fully" hydrated Mg 2+ ions, two possible mechanisms of stabilizing stem 1 are proposed. In both these cases Mg2+ ions play a critical role in stabilizing stem 1, either by directly forming a salt bridge between the strands of stem 1 or by stabilizing parallel orientation of the strands in stem 1, respectively. These findings explain the unexpected drop in frameshifting efficiency to null levels of the C8U mutant in a manner consistent with experimental observations.

AB - Using mechanical unfolding by optical tweezers (OT) and steered molecular dynamics (SMD) simulations, we have demonstrated the critical role of Mg 2+ ions for the resistance of the Beet Western Yellow Virus (BWYV) pseudoknot (PK) to unfolding. The two techniques were found to be complementary, providing information at different levels of molecular scale. Findings from the OT experiments indicated a critical role of stem 1 for unfolding of the PK, which was confirmed in the SMD simulations. The unfolding pathways of wild type and mutant appeared to depend upon pH and nucleotide sequence. SMD simulations support the notion that the stability of stem 1 is critical for -1 frameshifting. The all-atom scale nature of the SMD enabled clarification of the precise role of two Mg2+ ions, Mg45 and Mg52, as identified in the BWYV X-ray crystallography structure, in -1 frameshifting. On the basis of simulations with "partially" and "fully" hydrated Mg 2+ ions, two possible mechanisms of stabilizing stem 1 are proposed. In both these cases Mg2+ ions play a critical role in stabilizing stem 1, either by directly forming a salt bridge between the strands of stem 1 or by stabilizing parallel orientation of the strands in stem 1, respectively. These findings explain the unexpected drop in frameshifting efficiency to null levels of the C8U mutant in a manner consistent with experimental observations.

UR - http://www.scopus.com/inward/record.url?scp=79959503033&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959503033&partnerID=8YFLogxK

U2 - 10.1021/ja111281f

DO - 10.1021/ja111281f

M3 - Article

C2 - 21598975

AN - SCOPUS:79959503033

VL - 133

SP - 9775

EP - 9782

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 25

ER -