The serine protease domain of MASP-3: enzymatic properties and crystal structure in complex with ecotin

Mannan-binding lectin (MBL), ficolins and collectin-11 are known to associate with three homologous modular proteases, the MBL-Associated Serine Proteases (MASPs). The crystal structures of the catalytic domains of MASP-1 and MASP-2 have been solved, but the structure of the corresponding domain of...

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Bibliographic Details
Published in:PloS one 2013-07, Vol.8 (7), p.e67962-e67962
Main Authors: Gaboriaud, Christine, Gupta, Rajesh Kumar, Martin, Lydie, Lacroix, Monique, Serre, Laurence, Teillet, Florence, Arlaud, Gérard J, Rossi, Véronique, Thielens, Nicole M
Format: Article
Language:English
Subjects:
Alternatives
Analysis
Binding Sites
Biochemistry
Biochemistry, Molecular Biology
Biology
Catalysis
Catalytic Domain
Complement C1r - chemistry
Complement C1s - chemistry
Coumarins
Crystal structure
Crystallography, X-Ray
Crystals
Developmental disabilities
E coli
Enzymatic analysis
Enzyme Assays
Escherichia coli Proteins - chemistry
Ficolins
Fluorescence
Fluorescent Dyes
Homology
Humans
Interfaces
Irritable bowel syndrome
Lectins
Life Sciences
Mannan
Mannan-binding lectin
Mannose-binding lectin
Mannose-Binding Protein-Associated Serine Proteases - chemistry
Mannose-Binding Protein-Associated Serine Proteases - genetics
Mannose-binding protein-associated serine proteinase
MASP-1 protein
MASP-2 protein
Modular structures
Molecular Docking Simulation
Molecular structure
Mutation
Neurons and Cognition
Periplasmic Proteins - chemistry
Proenzymes
Properties (attributes)
Protease
Proteases
Protein Binding
Protein Interaction Domains and Motifs
Protein Multimerization
Proteins
Recombinant Proteins - chemistry
Recombinant Proteins - genetics
Serine
Serine proteinase
Structural Biology
Structure
Substrate Specificity
Substrates
Thrombin - chemistry
Trypsin
Trypsin - chemistry
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Summary:Mannan-binding lectin (MBL), ficolins and collectin-11 are known to associate with three homologous modular proteases, the MBL-Associated Serine Proteases (MASPs). The crystal structures of the catalytic domains of MASP-1 and MASP-2 have been solved, but the structure of the corresponding domain of MASP-3 remains unknown. A link between mutations in the MASP1/3 gene and the rare autosomal recessive 3MC (Mingarelli, Malpuech, Michels and Carnevale,) syndrome, characterized by various developmental disorders, was discovered recently, revealing an unexpected important role of MASP-3 in early developmental processes. To gain a first insight into the enzymatic and structural properties of MASP-3, a recombinant form of its serine protease (SP) domain was produced and characterized. The amidolytic activity of this domain on fluorescent peptidyl-aminomethylcoumarin substrates was shown to be considerably lower than that of other members of the C1r/C1s/MASP family. The E. coli protease inhibitor ecotin bound to the SP domains of MASP-3 and MASP-2, whereas no significant interaction was detected with MASP-1, C1r and C1s. A tetrameric complex comprising an ecotin dimer and two MASP-3 SP domains was isolated and its crystal structure was solved and refined to 3.2 Å. Analysis of the ecotin/MASP-3 interfaces allows a better understanding of the differential reactivity of the C1r/C1s/MASP protease family members towards ecotin, and comparison of the MASP-3 SP domain structure with those of other trypsin-like proteases yields novel hypotheses accounting for its zymogen-like properties in vitro.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0067962