The serine protease domain of MASP-3: enzymatic properties and crystal structure in complex with ecotin. - Archive ouverte HAL Access content directly
Journal Articles PLoS ONE Year : 2013

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

(1) , (1) , (1) , (1) , (2) , (1) , (1) , (1) , (1)
1
2

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.
Fichier principal
Vignette du fichier
Gaboriaud-2013_The_serine_AO_1_.pdf (3.57 Mo) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Loading...

Dates and versions

inserm-00868926 , version 1 (02-10-2013)

Identifiers

Cite

Christine Gaboriaud, Rajesh Kumar Gupta, Lydie Martin, Monique Lacroix, Laurence Serre, et al.. The serine protease domain of MASP-3: enzymatic properties and crystal structure in complex with ecotin.. PLoS ONE, 2013, 8 (7), pp.e67962. ⟨10.1371/journal.pone.0067962⟩. ⟨inserm-00868926⟩
578 View
423 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More