The hemopexin and O-glycosylated domains tune gelatinase B/MMP-9 bioavailability via inhibition and binding to cargo receptors.
Gelatinase B/matrix metalloproteinase-9 (MMP-9), a key regulator and effector of immunity, contains a C-terminal hemopexin domain preceded by a unique linker sequence of approximately 64 amino acid residues. This linker sequence is demonstrated to be an extensively O-glycosylated (OG) domain with a...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2006
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| _version_ | 1826299550864769024 |
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| author | Van den Steen, P Van Aelst, I Hvidberg, V Piccard, H Fiten, P Jacobsen, C Moestrup, S Fry, S Royle, L Wormald, M Wallis, R Rudd, P Dwek, R Opdenakker, G |
| author_facet | Van den Steen, P Van Aelst, I Hvidberg, V Piccard, H Fiten, P Jacobsen, C Moestrup, S Fry, S Royle, L Wormald, M Wallis, R Rudd, P Dwek, R Opdenakker, G |
| author_sort | Van den Steen, P |
| collection | OXFORD |
| description | Gelatinase B/matrix metalloproteinase-9 (MMP-9), a key regulator and effector of immunity, contains a C-terminal hemopexin domain preceded by a unique linker sequence of approximately 64 amino acid residues. This linker sequence is demonstrated to be an extensively O-glycosylated (OG) domain with a compact three-dimensional structure. The OG and hemopexin domains have no influence on the cleavage efficiency of MMP-9 substrates. In contrast, the hemopexin domain contains a binding site for the cargo receptor low density lipoprotein receptor-related protein-1 (LRP-1). Furthermore, megalin/LRP-2 is identified as a new functional receptor for the hemopexin domain of MMP-9, able to mediate the endocytosis and catabolism of the enzyme. The OG domain is required to correctly orient the hemopexin domain for inhibition by TIMP-1 and internalization by LRP-1 and megalin. Therefore, the OG and hemopexin domains down-regulate the bioavailability of active MMP-9 and the interactions with the cargo receptors are proposed to be the original function of hemopexin domains in MMPs. |
| first_indexed | 2024-03-07T05:03:38Z |
| format | Journal article |
| id | oxford-uuid:d92bb35d-c1d8-4e60-a158-fc3d8941f606 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:03:38Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:d92bb35d-c1d8-4e60-a158-fc3d8941f6062022-03-27T08:54:00ZThe hemopexin and O-glycosylated domains tune gelatinase B/MMP-9 bioavailability via inhibition and binding to cargo receptors.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d92bb35d-c1d8-4e60-a158-fc3d8941f606EnglishSymplectic Elements at Oxford2006Van den Steen, PVan Aelst, IHvidberg, VPiccard, HFiten, PJacobsen, CMoestrup, SFry, SRoyle, LWormald, MWallis, RRudd, PDwek, ROpdenakker, GGelatinase B/matrix metalloproteinase-9 (MMP-9), a key regulator and effector of immunity, contains a C-terminal hemopexin domain preceded by a unique linker sequence of approximately 64 amino acid residues. This linker sequence is demonstrated to be an extensively O-glycosylated (OG) domain with a compact three-dimensional structure. The OG and hemopexin domains have no influence on the cleavage efficiency of MMP-9 substrates. In contrast, the hemopexin domain contains a binding site for the cargo receptor low density lipoprotein receptor-related protein-1 (LRP-1). Furthermore, megalin/LRP-2 is identified as a new functional receptor for the hemopexin domain of MMP-9, able to mediate the endocytosis and catabolism of the enzyme. The OG domain is required to correctly orient the hemopexin domain for inhibition by TIMP-1 and internalization by LRP-1 and megalin. Therefore, the OG and hemopexin domains down-regulate the bioavailability of active MMP-9 and the interactions with the cargo receptors are proposed to be the original function of hemopexin domains in MMPs. |
| spellingShingle | Van den Steen, P Van Aelst, I Hvidberg, V Piccard, H Fiten, P Jacobsen, C Moestrup, S Fry, S Royle, L Wormald, M Wallis, R Rudd, P Dwek, R Opdenakker, G The hemopexin and O-glycosylated domains tune gelatinase B/MMP-9 bioavailability via inhibition and binding to cargo receptors. |
| title | The hemopexin and O-glycosylated domains tune gelatinase B/MMP-9 bioavailability via inhibition and binding to cargo receptors. |
| title_full | The hemopexin and O-glycosylated domains tune gelatinase B/MMP-9 bioavailability via inhibition and binding to cargo receptors. |
| title_fullStr | The hemopexin and O-glycosylated domains tune gelatinase B/MMP-9 bioavailability via inhibition and binding to cargo receptors. |
| title_full_unstemmed | The hemopexin and O-glycosylated domains tune gelatinase B/MMP-9 bioavailability via inhibition and binding to cargo receptors. |
| title_short | The hemopexin and O-glycosylated domains tune gelatinase B/MMP-9 bioavailability via inhibition and binding to cargo receptors. |
| title_sort | hemopexin and o glycosylated domains tune gelatinase b mmp 9 bioavailability via inhibition and binding to cargo receptors |
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