4IW4

Crystal structure of the serine protease domain of MASP-3 in complex with ecotin

Summary for 4IW4

• Entry DOI: 10.2210/pdb4iw4/pdb
• Related: 3DEM
• Descriptor: Ecotin, Mannan-binding lectin serine protease 3 (3 entities in total)
• Functional Keywords: trypsin-like fold, protease, inhibitor, extracellular, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P23827; Periplasm: P48740
• Total number of polymer chains: 4
• Total formula weight: 93409.96

Authors

Gaboriaud, C. (deposition date: 2013-01-23, release date: 2013-06-19, Last modification date: 2024-10-09)

Primary citation

Gaboriaud, C.,Gupta, R.K.,Martin, L.,Lacroix, M.,Serre, L.,Teillet, F.,Arlaud, G.J.,Rossi, V.,Thielens, N.M.
The Serine Protease Domain of MASP-3: Enzymatic Properties and Crystal Structure in Complex with Ecotin.
Plos One, 8:e67962-e67962, 2013

PubMed Abstract: 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.

PubMed: 23861840
DOI: 10.1371/journal.pone.0067962

Experimental method

X-RAY DIFFRACTION (3.2 Å)