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PDBsum entry 4aqb
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Blood clotting
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PDB id
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4aqb
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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 and functional characterization of the complement regulator mannose-Binding lectin (mbl)/ficolin-Associated protein-1 (map-1).
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Authors
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M.O.Skjoedt,
P.Roversi,
T.Hummelshøj,
Y.Palarasah,
A.Rosbjerg,
S.Johnson,
S.M.Lea,
P.Garred.
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Ref.
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J Biol Chem, 2012,
287,
32913-32921.
[DOI no: ]
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PubMed id
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Abstract
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The human lectin complement pathway activation molecules comprise
mannose-binding lectin (MBL) and ficolin-1, -2, and -3 in complex with
associated serine proteases MASP-1, -2, and -3 and the non-enzymatic small MBL
associated protein or sMAP. Recently, a novel plasma protein named
MBL/ficolin-associated protein-1 (MAP-1) was identified in humans. This protein
is the result of a differential splicing of the MASP1 gene and includes the
major part of the heavy chain but lacks the serine protease domain. We
investigated the direct interactions of MAP-1 and MASP-3 with ficolin-3 and MBL
using surface plasmon resonance and found affinities around 5 nm and 2.5 nm,
respectively. We studied structural aspects of MAP-1 and could show by
multi-angle laser light scattering that MAP-1 forms a calcium-dependent
homodimer in solution. We were able to determine the crystal structure of MAP-1,
which also contains a head-to-tail dimer ∼146 Å long. This structure of
MAP-1 also enables modeling and assembly of the MASP-1 molecule in its entirety.
Finally we found that MAP-1 competes with all three MASPs for ligand binding and
is able to mediate a strong dose-dependent inhibitory effect on the lectin
pathway activation, as measured by levels of C3 and C9.
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