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PDBsum entry 1vvd
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Complement inhibitor
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PDB id
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1vvd
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References listed in PDB file
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Key reference
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Title
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Nmr studies of a viral protein that mimics the regulators of complement activation.
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Authors
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A.P.Wiles,
G.Shaw,
J.Bright,
A.Perczel,
I.D.Campbell,
P.N.Barlow.
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Ref.
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J Mol Biol, 1997,
272,
253-265.
[DOI no: ]
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PubMed id
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Abstract
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Vaccinia virus complement control protein (VCP) is a 243-residue protein that is
similar in sequence to the regulators of complement activation; its role is to
defend the virus against attack by the host complement system. A fragment of
this protein spanning the two complement protein (CP)-modules (residues 126 to
243) which make up the C-terminal half of VCP has been expressed in Pichia
pastoris. A 15N-labelled sample was purified for the purposes of structure
determination and measurements of dynamics in solution using NMR. Structures
were calculated on the basis of 1767 NMR-derived distance and angle restraints,
with a longer than normal high-temperature simulated annealing (SA) protocol
which improved convergence. The viral CP-modules are structurally very similar
to the 15th and 16th CP-modules of human factor H (fH; average r.m.s.d., for
invariant Trp and Cys, four pair-wise comparisons,=1.2 A) but less similar to
the fifth CP-module of fH (average r.m.s.d.=2.2 A). In the VCP fragment, the
orientation of one module with respect to the other is clearly defined by the
experimental data, and T1 measurements are consistent with only limited
flexibility at the module-module interface. The r.m.s.d. over all of the 118
residues (backbone atoms) is 0.73 A. The intermodular orientation is better
defined than, and significantly different from, that observed in a CP-module
pair from fH (re-calculated using the extended SA protocol). In VCP the long
axis of the second module is tilted by 59(+/-4) degrees with respect to the
first module (50(+/-13) degrees in the fH pair), and twisted with respect to the
first module by 22(+/-6) degrees (223(+/-17) degrees in fH). The differences
between the human and viral proteins may be rationalised in terms of the lack of
hydrogen-bond stabilised secondary structure in the N-terminal portion of fH
module 16, and the number and type of amino acid side-chains which make up the
interface. A similar intermodular interface may be predicted between the third
and fourth module of human C4 binding protein and, probably, between the third
and fourth modules of the guinea pig acrosomal matrix protein 67; but the
formulation of general rules for predicting the structure of interfaces between
CP-modules awaits further experimental data.
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Figure 7.
Figure 7. Topological similarity amongst members of
the CP-module family. An overlay of all five CP-mod-
ules for which detailed tertiary structures are now avail-
able (all overlaid on fH15 using the alpha and beta
carbon atoms of the invariant Trp and Cys residues).
The backbones are shown as ribbons. The left-hand dia-
gram emphasises the backbone (thick ribbon); the right-
hand diagram shows the overlay of invariant Trp and
Cys residues (stick representation). Key: red, H5;
magenta, H15; yellow, H16; cyan, VCP3; white, VCP4.
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Figure 8.
Figure 8. A comparison of human and viral proteins.
A MOLSCRIPT (Kraulis, 1991) representation of the two
CP-module pairs for which three-dimensional structures
are now available. Refined and minimised average
structures are shown. The tryptophan residues are
shown as a CPK surface.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1997,
272,
253-265)
copyright 1997.
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