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PDBsum entry 2c8i
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Virus/receptor
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PDB id
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2c8i
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Contents |
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289 a.a.*
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252 a.a.*
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238 a.a.*
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60 a.a.*
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252 a.a.*
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* C-alpha coords only
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References listed in PDB file
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Key reference
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Title
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Structural and functional insights into the interaction of echoviruses and decay-Accelerating factor.
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Authors
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D.M.Pettigrew,
D.T.Williams,
D.Kerrigan,
D.J.Evans,
S.M.Lea,
D.Bhella.
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Ref.
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J Biol Chem, 2006,
281,
5169-5177.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
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Abstract
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Many enteroviruses bind to the complement control protein decay-accelerating
factor (DAF) to facilitate cell entry. We present here a structure for echovirus
(EV) type 12 bound to DAF using cryo-negative stain transmission electron
microscopy and three-dimensional image reconstruction to 16-A resolution, which
we interpreted using the atomic structures of EV11 and DAF. DAF binds to a
hypervariable region of the capsid close to the 2-fold symmetry axes in an
interaction that involves mostly the short consensus repeat 3 domain of DAF and
the capsid protein VP2. A bulge in the density for the short consensus repeat 3
domain suggests that a loop at residues 174-180 rearranges to prevent steric
collision between closely packed molecules at the 2-fold symmetry axes. Detailed
analysis of receptor interactions between a variety of echoviruses and DAF using
surface plasmon resonance and comparison of this structure (and our previous
work; Bhella, D., Goodfellow, I. G., Roversi, P., Pettigrew, D., Chaudhry, Y.,
Evans, D. J., and Lea, S. M. (2004) J. Biol. Chem. 279, 8325-8332) with
reconstructions published for EV7 bound to DAF support major differences in
receptor recognition among these viruses. However, comparison of the electron
density for the two virus.receptor complexes (rather than comparisons of the
pseudo-atomic models derived from fitting the coordinates into these densities)
suggests that the dramatic differences in interaction affinities/specificities
may arise from relatively subtle structural differences rather than from
large-scale repositioning of the receptor with respect to the virus surface.
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Figure 1.
FIGURE 1. Stereo views of surface-rendered
three-dimensional reconstructions of unlabeled and DAF-labeled
EV12. A, 14-Å resolution reconstruction of unlabeled EV12.
B, reconstruction of EV12 bound to DAF[34] at 16-Å
resolution showing clear density that we attribute to the
two-domain receptor fragment; C, additional density seen in the
16-Å resolution reconstruction of EV12 bound to all four
SCR domains of DAF.
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Figure 2.
FIGURE 2. Calculation of a quasi-atomic model for
EV12·DAF. A, variation in SCR2 orientation for the 14
crystal forms of DAF[1234], with each model superimposed onto
the capsid-docked SCR3. Only SCR2 is shown for each model. B,
variation in SCR2 orientation for the 43 different NMR models.
C, the optimal SCR2 position is from chain B of the x-ray
structure of Protein Data Bank code 1OK3 [PDB]
. D, points of contact on DAF[1234] with the symmetry partner
across the 2-fold axis. The green surface represents a steric
clash between Arg^102 and Arg^103 and identical residues of the
symmetry partner. This is resolved by side chain rearrangement.
The blue surface is a van der Waals contact between Pro^137 and
Pro^109 of the symmetry partner. The red and orange surfaces are
an overlap between the main chain atoms of residues 174-180 of
SCR3 (red) and a surface composed of residues 95-98 and 75-77 of
the symmetry partner SCR2 (orange). This clash can be resolved
only by a remodeling of loop 174-180. E, electron density of
SCR1. The strong density at the center of each lobe is shown as
a red mesh, whereas the lower contours are shown as a blue mesh.
The major and minor lobes, as well as the position of SCR2, are
highlighted. F, superposition of all 14 possible SCR1
orientations from the crystal structures. These orientations are
consistent only with the minor lobe density. G, optimal "minor
lobe" SCR1 model from the side. Also highlighted is the
remodeled loop 174-180 on SCR3. H, complete DAF model based on a
hybrid of the original DAF[34] fit (with the remodeled loop
174-180 on SCR3) and the two crystal structures that gave
optimal SCR1 and SCR2 positions (green). Also shown in magenta
is the alternative position for SCR1 proposed to explain the
major lobe density. The symmetry partner DAF molecule is shown
in red. I, radially depth-cued atomic model of the virus capsid
(blue) decorated with 60 copies of the DAF[1234] hybrid model
(green).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
5169-5177)
copyright 2006.
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Secondary reference #1
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Title
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The structure of echovirus type 12 bound to a two-Domain fragment of its cellular attachment protein decay-Accelerating factor (cd 55).
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Authors
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D.Bhella,
I.G.Goodfellow,
P.Roversi,
D.Pettigrew,
Y.Chaudhry,
D.J.Evans,
S.M.Lea.
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Ref.
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J Biol Chem, 2004,
279,
8325-8332.
[DOI no: ]
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PubMed id
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Figure 2.
FIG. 2. Stereo pairs of surface rendered three-dimensional
reconstructions of unlabeled EV12 virions (A) and
DAF[34]-labeled virions (B). Isosurfaces of these
reconstructions are merged and rendered in their respective
color schemes to highlight the differences in density attributed
to the two SCR domain fragment of DAF (C). A low resolution
representation of EV7 bound to DAF[1234], derived from PDB code
1M11 [PDB]
(30), highlights the differently oriented densities in these two
complexes (D). In this model the densities of two copies of
DAF[1234] are superimposed, laying across the virion 2-fold
symmetry axes, giving rise to a hybrid density representing the
two possible positions for the molecule. A radial depth-cue
color scheme is used to indicate distance from the center of the
virion (see the key).
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Figure 5.
FIG. 5. A comparison of the low resolution
three-dimensional reconstruction of EV12-DAF[34] (A) and a
space-filling representation of the EV12-DAF[34] complex (B),
generated using the crystallographic co-ordinates for EV11 and
DAF[34]. Radial depth-cueing emphasizes the distance between
atoms or regions of density and the center of the virion such
that dark colors are close to the center and light colors are
farther away. EV12 (and EV11) is colored in shades of blue,
whereas DAF[34] is colored in green. A space-filling
representation of the EV7-DAF[1234] complex (30) (C) highlights
the different orientation of DAF bound to these two viruses. The
model deposited under PDB code 1M11 [PDB]
contains  -carbon atoms only;
this view is therefore rendered with the atomic radii for each
atom set to 3.5Å. EV7 is colored in shades of purple, and
the receptor is in red. A close-up view of DAF[34] shown as in
panel B but rotated 180^o about a vertical axis exposes the
residues buried in the virus-receptor complex (D). Residues are
colored according to their contribution to the total contact
area (  840 Å2); yellow (1
< 5%), orange (5 < 9%), and red (9%+). A close-up view of EV11
without the receptor in place exposes buried residues on the
surface of the capsid that are colored according to the same
scheme (E); the biological protomer is indicated.
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The above figures are
reproduced from the cited reference
with permission from the ASBMB
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Headers
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