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PDBsum entry 1q0p
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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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Crystal structure of the a domain from complement factor b reveals an integrin-Like open conformation.
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Authors
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A.A.Bhattacharya,
M.L.Lupher,
D.E.Staunton,
R.C.Liddington.
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Ref.
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Structure, 2004,
12,
371-378.
[DOI no: ]
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PubMed id
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Abstract
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Complement factor B is a 90 kDa protein consisting of three domains: a
three-module complement control protein, a von Willebrand factor A domain, and a
C-terminal serine protease (SP) domain that adopts a default inactive (zymogen)
conformation. The interaction between factor B and pathogen-bound C3b is
mediated by its A domain, triggering a conformational change in factor B that
ultimately creates the "C3 convertase" of the alternative complement
pathway. We report the crystal structure of the A domain from factor B and show
that it contains an integrin-like MIDAS motif that adopts the "open"
conformation typical of integrin-ligand complexes, with an acidic residue
(provided by a fortuitous crystal contact) completing the coordination of the
metal ion. Modeling studies indicate that the factor B A domain can also adopt
the closed conformation, supporting the hypothesis that an "integrin-like
switch" is conserved in complement proteins and perhaps in 60 other A
domains found within the human proteome.
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Figure 3.
Figure 3. Conformation of the MIDAS Motif and the bF-a7
Turn(A) Superposition of the MIDAS motifs of factor B and a2
integrin A domains. The structures are superposed on their
central b sheets. Color-coding is as follows: factor B Ca,
green; side chains, black; ligand mimetic, gold and red; a2 A
domain Ca and side chains, white (semitransparent). The metal
ion ("M") is in purple, with coordinating oxygens from S253,
S255, T328, and two water molecules ("W") in red. The side
chains of D251 and D364 form water-mediated bonds to the metal
ion.(B) Overlay of the bF-a7 turns of factor B (red) with the
open (translucent green) and closed (yellow) conformations of
the integrin aM I domain. The Ca positions of analogous residues
(M433 in factor B; F302 in aM) are indicated.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2004,
12,
371-378)
copyright 2004.
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