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PDBsum entry 1nwv
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Biosynthetic protein
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PDB id
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1nwv
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Solution structure of a functionally active fragment of decay-Accelerating factor.
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Authors
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S.Uhrinova,
F.Lin,
G.Ball,
K.Bromek,
D.Uhrin,
M.E.Medof,
P.N.Barlow.
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Ref.
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Proc Natl Acad Sci U S A, 2003,
100,
4718-4723.
[DOI no: ]
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PubMed id
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Abstract
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The second and third modules of human decay accelerating factor (DAF) are
necessary and sufficient to accelerate decay of the classical pathway (CP)
convertase of complement. No structure of a mammalian protein with
decay-accelerating activity has been available to date. We therefore determined
the solution structure of DAF modules 2 and 3 (DAF approximately 2,3).
Structure-guided analysis of 24 mutants identified likely contact points between
DAF and the CP convertase. Three (R96, R69, and a residue in the vicinity of
L171) lie on DAF approximately 2,3's concave face. A fourth, consisting of K127
and nearby R100, is on the opposite face. Regions of module 3 remote from the
semiflexible 2-3 interface seem not to be involved in binding to the CP
convertase. DAF thus seems to occupy a groove on the CP convertase such that
both faces of DAF close to the 2-3 junction (including a positively charged
region that encircles the protein at this point) interact simultaneously.
Alternative pathway convertase interactions with DAF require additional regions
of CCP 3 lying away from the 2-3 interface, consistent with the established
additional requirement of module 4 for alternative pathway regulation.
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Figure 2.
Fig 2. The solution structure of DAF  2,3. (a) Overlay
(backbone trace) of 42 lowest energy structures on selected
CCP-3 C  s of structure closest to
the mean. (b) As in a but structures overlaid on selected C s of
CCP-2. (c) MOLSCRIPT trace (showing Cys and Trp) of structure
with intermodular angles closest to average; hv, hypervariable
loop; loops, turns, and bulges are labeled with aa numbers;
strands are annotated as in Fig. 1.
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Figure 3.
Fig 3. Intermodular angles in DAF 2,3. (a) Distribution of
tilt (filled), twist (gray), and skew (open) angles for the 42
lowest energy structures [definition of angles (34) summarized
in Inset]. (b) Angles plotted by using polar coordinates; each
wedge summarizes mean ± SD for the angle indicated.
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