4aqb
From Proteopedia
MBL-Ficolin Associated Protein-1, MAP-1 aka MAP44
Structural highlights
Disease[MASP1_HUMAN] Defects in MASP1 are the cause of 3MC syndrome type 1 (3MC1) [MIM:257920]. 3MC1 is a disorder characterized by facial dysmorphism that includes hypertelorism, blepharophimosis, blepharoptosis and highly arched eyebrows, cleft lip and/or palate, craniosynostosis, learning disability and genital, limb and vesicorenal anomalies. The term 3MC syndrome includes Carnevale, Mingarelli, Malpuech, and Michels syndromes.[1] Function[MASP1_HUMAN] Functions in the lectin pathway of complement, which performs a key role in innate immunity by recognizing pathogens through patterns of sugar moieties and neutralizing them. The lectin pathway is triggered upon binding of mannan-binding lectin (MBL) and ficolins to sugar moieties which leads to activation of the associated proteases MASP1 and MASP2. Functions as an endopeptidase and may activate MASP2 or C2 or directly activate C3 the key component of complement reaction. Isoform 2 may have an inhibitory effect on the activation of the lectin pathway of complement or may cleave IGFBP5.[2] [3] Publication Abstract from PubMedThe 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 approximately 146 A 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. Crystal Structure and Functional Characterization of the Complement Regulator Mannose-binding Lectin (MBL)/Ficolin-associated Protein-1 (MAP-1).,Skjoedt MO, Roversi P, Hummelshoj T, Palarasah Y, Rosbjerg A, Johnson S, Lea SM, Garred P J Biol Chem. 2012 Sep 21;287(39):32913-21. Epub 2012 Aug 1. PMID:22854970[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Garred, P | Hummelshoj, T | Johnson, S | Lea, S M | Palarasah, Y | Roversi, P | Skjoedt, M O | Blood clotting | Complement | Ficolin | Lectin complement pathway | Mannan-binding protein | Mannose- binding lectin | Map1 | Map44 | Mbl/ficolin associated protein-1 | Mbl/ficolin associated serine protease
