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PDBsum entry 3dem
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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 cub1-Egf-Cub2 domain of human masp-1/3 and identification of its interaction sites with mannan-Binding lectin and ficolins.
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Authors
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F.Teillet,
C.Gaboriaud,
M.Lacroix,
L.Martin,
G.J.Arlaud,
N.M.Thielens.
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Ref.
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J Biol Chem, 2008,
283,
25715-25724.
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PubMed id
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Abstract
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MASP-1 and MASP-3 are homologous proteases arising from alternative splicing of
the MASP1/3 gene. They include an identical CUB(1)-EGF-CUB(2)-CCP(1)-CCP(2)
module array prolonged by different serine protease domains at the C-terminal
end. The x-ray structure of the CUB(1)-EGF-CUB(2) domain of human MASP-1/3,
responsible for interaction of MASP-1 and -3 with their partner proteins
mannan-binding lectin (MBL) and ficolins, was solved to a resolution of 2.3A(.)
The structure shows a head-to-tail homodimer mainly stabilized by hydrophobic
interactions between the CUB(1) module of one monomer and the epidermal growth
factor (EGF) module of its counterpart. A Ca(2+) ion bound primarily to both EGF
modules stabilizes the intra- and inter-monomer CUB(1)-EGF interfaces.
Additional Ca(2+) ions are bound to each CUB(1) and CUB(2) module through six
ligands contributed by Glu(49), Asp(57), Asp(102), and Ser(104) (CUB(1)) and
their counterparts Glu(216), Asp(226), Asp(263), and Ser(265) (CUB(2)), plus one
and two water molecules, respectively. To identify the residues involved in
interaction of MASP-1 and -3 with MBL and L- and H-ficolins, 27 point mutants of
human MASP-3 were generated, and their binding properties were analyzed using
surface plasmon resonance spectroscopy. These mutations map two homologous
binding sites contributed by modules CUB(1) and CUB(2), located in close
vicinity of their Ca(2+)-binding sites and stabilized by the Ca(2+) ion. This
information allows us to propose a model of the MBL-MASP-1/3 interaction,
involving a major electrostatic interaction between two acidic Ca(2+) ligands of
MASP-1/3 and a conserved lysine of MBL. Based on these and other data, a
schematic model of a MBL.MASP complex is proposed.
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