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...
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/2ea285bc38a541dab068aabef65228e2 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:2ea285bc38a541dab068aabef65228e2 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:2ea285bc38a541dab068aabef65228e22021-11-18T07:38:33ZThe serine protease domain of MASP-3: enzymatic properties and crystal structure in complex with ecotin.1932-620310.1371/journal.pone.0067962https://doaj.org/article/2ea285bc38a541dab068aabef65228e22013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23861840/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Mannan-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.Christine GaboriaudRajesh Kumar GuptaLydie MartinMonique LacroixLaurence SerreFlorence TeilletGérard J ArlaudVéronique RossiNicole M ThielensPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e67962 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Christine Gaboriaud Rajesh Kumar Gupta Lydie Martin Monique Lacroix Laurence Serre Florence Teillet Gérard J Arlaud Véronique Rossi Nicole M Thielens The serine protease domain of MASP-3: enzymatic properties and crystal structure in complex with ecotin. |
| description |
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. |
| format |
article |
| author |
Christine Gaboriaud Rajesh Kumar Gupta Lydie Martin Monique Lacroix Laurence Serre Florence Teillet Gérard J Arlaud Véronique Rossi Nicole M Thielens |
| author_facet |
Christine Gaboriaud Rajesh Kumar Gupta Lydie Martin Monique Lacroix Laurence Serre Florence Teillet Gérard J Arlaud Véronique Rossi Nicole M Thielens |
| author_sort |
Christine Gaboriaud |
| title |
The serine protease domain of MASP-3: enzymatic properties and crystal structure in complex with ecotin. |
| title_short |
The serine protease domain of MASP-3: enzymatic properties and crystal structure in complex with ecotin. |
| title_full |
The serine protease domain of MASP-3: enzymatic properties and crystal structure in complex with ecotin. |
| title_fullStr |
The serine protease domain of MASP-3: enzymatic properties and crystal structure in complex with ecotin. |
| title_full_unstemmed |
The serine protease domain of MASP-3: enzymatic properties and crystal structure in complex with ecotin. |
| title_sort |
serine protease domain of masp-3: enzymatic properties and crystal structure in complex with ecotin. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/2ea285bc38a541dab068aabef65228e2 |
| work_keys_str_mv |
AT christinegaboriaud theserineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT rajeshkumargupta theserineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT lydiemartin theserineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT moniquelacroix theserineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT laurenceserre theserineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT florenceteillet theserineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT gerardjarlaud theserineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT veroniquerossi theserineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT nicolemthielens theserineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT christinegaboriaud serineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT rajeshkumargupta serineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT lydiemartin serineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT moniquelacroix serineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT laurenceserre serineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT florenceteillet serineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT gerardjarlaud serineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT veroniquerossi serineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin AT nicolemthielens serineproteasedomainofmasp3enzymaticpropertiesandcrystalstructureincomplexwithecotin |
| _version_ |
1718423150420557824 |