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Solution structure of the apical stem-loop of the human hepatitis B virus encapsidation signal

Flodell, Sara ; Petersen, Michael ; Girard, Frederic ; Zdunek, Janusz ; Kidd-Ljunggren, Karin LU ; Schleucher, Jurgen and Wijmenga, Sybren (2006) In Nucleic Acids Research 34(16). p.4449-4457
Abstract
Hepatitis B virus (HBV) replication is initiated by HBV RT binding to the highly conserved encapsidation signal, epsilon, at the 5' end of the RNA pregenome. Epsilon contains an apical stem-loop, whose residues are either totally conserved or show rare non-disruptive mutations. Here we present the structure of the apical stem-loop based on NOE, RDC and H-1 chemical shift NMR data. The H-1 chemical shifts proved to be crucial to define the loop conformation. The loop sequence 5'-CUGUGC-3' folds into a UGU triloop with a CG closing base pair and a bulged out C and hence forms a pseudo-triloop, a proposed protein recognition motif. In the UGU loop conformations most consistent with experimental data, the guanine nucleobase is located on the... (More)
Hepatitis B virus (HBV) replication is initiated by HBV RT binding to the highly conserved encapsidation signal, epsilon, at the 5' end of the RNA pregenome. Epsilon contains an apical stem-loop, whose residues are either totally conserved or show rare non-disruptive mutations. Here we present the structure of the apical stem-loop based on NOE, RDC and H-1 chemical shift NMR data. The H-1 chemical shifts proved to be crucial to define the loop conformation. The loop sequence 5'-CUGUGC-3' folds into a UGU triloop with a CG closing base pair and a bulged out C and hence forms a pseudo-triloop, a proposed protein recognition motif. In the UGU loop conformations most consistent with experimental data, the guanine nucleobase is located on the minor groove face and the two uracil bases on the major groove face. The underlying helix is disrupted by a conserved non-paired U bulge. This U bulge adopts multiple conformations, with the nucleobase being located either in the major groove or partially intercalated in the helix from the minor groove side, and bends the helical stem. The pseudo-triloop motif, together with the U bulge, may represent important anchor points for the initial recognition of epsilon by the viral RT. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nucleic Acids Research
volume
34
issue
16
pages
4449 - 4457
publisher
Oxford University Press
external identifiers
  • wos:000241277200019
  • pmid:16945960
  • scopus:33749986531
ISSN
1362-4962
DOI
10.1093/nar/gkl582
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Division of Infection Medicine (SUS) (013008000)
id
383dd0de-bdff-48bd-9676-b498db032b1a (old id 387893)
date added to LUP
2016-04-01 11:42:17
date last changed
2021-09-22 04:51:37
@article{383dd0de-bdff-48bd-9676-b498db032b1a,
  abstract     = {Hepatitis B virus (HBV) replication is initiated by HBV RT binding to the highly conserved encapsidation signal, epsilon, at the 5' end of the RNA pregenome. Epsilon contains an apical stem-loop, whose residues are either totally conserved or show rare non-disruptive mutations. Here we present the structure of the apical stem-loop based on NOE, RDC and H-1 chemical shift NMR data. The H-1 chemical shifts proved to be crucial to define the loop conformation. The loop sequence 5'-CUGUGC-3' folds into a UGU triloop with a CG closing base pair and a bulged out C and hence forms a pseudo-triloop, a proposed protein recognition motif. In the UGU loop conformations most consistent with experimental data, the guanine nucleobase is located on the minor groove face and the two uracil bases on the major groove face. The underlying helix is disrupted by a conserved non-paired U bulge. This U bulge adopts multiple conformations, with the nucleobase being located either in the major groove or partially intercalated in the helix from the minor groove side, and bends the helical stem. The pseudo-triloop motif, together with the U bulge, may represent important anchor points for the initial recognition of epsilon by the viral RT.},
  author       = {Flodell, Sara and Petersen, Michael and Girard, Frederic and Zdunek, Janusz and Kidd-Ljunggren, Karin and Schleucher, Jurgen and Wijmenga, Sybren},
  issn         = {1362-4962},
  language     = {eng},
  number       = {16},
  pages        = {4449--4457},
  publisher    = {Oxford University Press},
  series       = {Nucleic Acids Research},
  title        = {Solution structure of the apical stem-loop of the human hepatitis B virus encapsidation signal},
  url          = {http://dx.doi.org/10.1093/nar/gkl582},
  doi          = {10.1093/nar/gkl582},
  volume       = {34},
  year         = {2006},
}