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PDBsum entry 2v1x
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References listed in PDB file
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Key reference
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Title
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Structure of the human recq1 helicase reveals a putative strand-Separation pin.
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Authors
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A.C.Pike,
B.Shrestha,
V.Popuri,
N.Burgess-Brown,
L.Muzzolini,
S.Costantini,
A.Vindigni,
O.Gileadi.
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Ref.
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Proc Natl Acad Sci U S A, 2009,
106,
1039-1044.
[DOI no: ]
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PubMed id
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Abstract
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RecQ-like helicases, which include 5 members in the human genome, are important
in maintaining genome integrity. We present a crystal structure of a truncated
form of the human RECQ1 protein with Mg-ADP. The truncated protein is active in
DNA fork unwinding but lacks other activities of the full-length enzyme:
disruption of Holliday junctions and DNA strand annealing. The structure of
human RECQ1 resembles that of Escherichia coli RecQ, with some important
differences. All structural domains are conserved, including the 2 RecA-like
domains and the RecQ-specific zinc-binding and winged-helix (WH) domains.
However, the WH domain is positioned at a different orientation from that of the
E. coli enzyme. We identify a prominent beta-hairpin of the WH domain as
essential for DNA strand separation, which may be analogous to DNA
strand-separation features of other DNA helicases. This hairpin is significantly
shorter in the E. coli enzyme and is not required for its helicase activity,
suggesting that there are significant differences between the modes of action of
RecQ family members.
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Figure 2.
Overview of RECQ1 structure. (A) Ribbon representation of a
single RECQ1 molecule, viewed from 3 perpendicular orientations.
The subdomains are identified by color: Core helicase domain D1,
red; core helicase domain D2, blue; zinc motif (ZnD), yellow;
helical hairpin (HH), orange; WH domain, green; and the
β-hairpin in purple. ADP is shown in space-filling form. (B) E.
coli RecQ, colored as in A. [PDB ID code 1OYY (30)] The molecule
is viewed in the same orientation as the central view in A,
using the D2 domain as a reference. (C) Side-by-side comparison
of bacterial RecQ (Left) and human RECQ1 (Right). Arrows
indicate the rotations of the various domains. The WH domain
rotates 90° around the vertical (compare orientation of
helix α1 marked by asterisk), the HH tilts up by 10°, and
the D1 rotates away from D2.
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Figure 3.
Details of the ADP and Zn-binding regions. (A) The
nucleotide-binding pocket. Main chain and carbons are colored
according the conserved motifs: motif 0 (yellow), motif I
(magenta), motif II (light blue), motif V (gray). (B) Overlay of
the Zn domains of RECQ1 (orange) and E. coli RecQ (gray). The
yellow/black spheres indicate the zinc ion, which nearly overlap
in the 2 structures. (C) Overlay of the WH domains of RECQ1
(red), WRN (blue), and E. coli RecQ (green). The β-hairpin
forming one of the wings and the hydrophobic residues at the
hairpin tip are highlighted.
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