4AQB

MBL-Ficolin Associated Protein-1, MAP-1 aka MAP44

Summary for 4AQB

• Entry DOI: 10.2210/pdb4aqb/pdb
• Descriptor: MANNAN-BINDING LECTIN SERINE PROTEASE 1, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: blood clotting, mannan-binding protein, complement, ficolins, lectin complement pathway, mannose- binding lectin, mbl/ficolin associated protein-1, mbl/ficolin associated serine proteases, map1, map44
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Secreted: P48740
• Total number of polymer chains: 1
• Total formula weight: 43360.89

Authors

Skjoedt, M.O.,Roversi, P.,Hummelshoj, T.,Palarasah, Y.,Johnson, S.,Lea, S.M.,Garred, P. (deposition date: 2012-04-16, release date: 2012-08-08, Last modification date: 2024-10-23)

Primary citation

Skjoedt, M.O.,Roversi, P.,Hummelshoj, T.,Palarasah, Y.,Rosbjerg, A.,Johnson, S.,Lea, S.M.,Garred, P.
Crystal Structure and Functional Characterization of the Complement Regulator Mannose-Binding Lectin (Mbl)/Ficolin-Associated Protein-1 (Map-1).
J.Biol.Chem., 287:32913-, 2012

PubMed Abstract: 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.

PubMed: 22854970
DOI: 10.1074/JBC.M112.386680

Experimental method

X-RAY DIFFRACTION (4.2 Å)