Van den Steen, Philippe E., Van Aelst, Ilse, Hvidberg, Vibeke, Piccard, Helene, Fiten, Pierre, Jacobsen, Christian, Moestrup, Soren K., Fry, Simon, Royle, Louise, Wormald, Mark R. , Wallis, Russell, Rudd , Pauline M., Dwek, Raymond A. and Opdenakker, Ghislain (2006) The hemopexin and O-glycosylated domains tune gelatinase B/MMP-9 bioavailability via inhibition and binding to cargo receptors. Journal of Biological Chemistry, 281 (27). pp. 18626-18637. ISSN 0021-9258Full text not available from this repository.
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 ?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.
|Subjects:||University of Westminster > Science and Technology > Life Sciences, School of (No longer in use)|
|Depositing User:||Rachel Wheelhouse|
|Date Deposited:||13 Mar 2012 14:51|
|Last Modified:||13 Mar 2012 14:51|
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