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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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PDB id:
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| Name: |
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Blood clotting
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Title:
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Mbl-ficolin associated protein-1, map-1 aka map44
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Structure:
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Mannan-binding lectin serine protease 1. Chain: a. Synonym: mbl-ficolin associated protein-1, complement factor masp-3, complement-activating component of ra-reactive factor, mannose- binding lectin-associated serine protease 1, masp-1, mannose-binding protein-associated serine protease, ra-reactive factor serine protease p100, rarf, serine protease 5, mannan-binding lectin serine protease 1 heavy chain. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Tissue: plasma. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: cho dg44.
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Resolution:
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4.20Å
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R-factor:
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0.280
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R-free:
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0.301
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Authors:
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M.O.Skjoedt,P.Roversi,T.Hummelshoj,Y.Palarasah,S.Johnson,S.M.Lea, P.Garred
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Key ref:
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M.O.Skjoedt
et al.
(2012).
Crystal structure and functional characterization of the complement regulator mannose-binding lectin (MBL)/ficolin-associated protein-1 (MAP-1).
J Biol Chem,
287,
32913-32921.
PubMed id:
DOI:
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Date:
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16-Apr-12
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Release date:
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08-Aug-12
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PROCHECK
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Headers
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References
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P48740
(MASP1_HUMAN) -
Mannan-binding lectin serine protease 1 from Homo sapiens
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Seq:
Struc:
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699 a.a.
345 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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*
PDB and UniProt seqs differ
at 3 residue positions (black
crosses)
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DOI no:
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J Biol Chem
287:32913-32921
(2012)
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PubMed id:
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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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M.O.Skjoedt,
P.Roversi,
T.Hummelshøj,
Y.Palarasah,
A.Rosbjerg,
S.Johnson,
S.M.Lea,
P.Garred.
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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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Links
