Title: Insights into the structure and domain flexibility of full-length pro-matrix metalloproteinase-9/gelatinase B
Authors: Rosenblum, Gabriel *
Van den Steen, Philippe *
Cohen, Sidney R *
Grossmann, J Günter
Frenkel, Jessica
Sertchook, Rotem
Slack, Nelle
Strange, Richard W
Opdenakker, Ghislain
Sagi, Irit # ×
Issue Date: Oct-2007
Publisher: Current Biology
Series Title: Structure vol:15 issue:10 pages:1227-1236
Abstract: The multidomain zinc endopeptidase matrix metalloproteinase-9 (MMP-9) is a recognized therapeutic target in autoimmune diseases, vascular pathologies, and cancer. Despite its importance, structural characterization of full-length pro-MMP-9 is incomplete. Here, we report the structural model of full-length pro-MMP-9 and, in particular, the molecular character of its unique proline-rich and heavily O-glycosylated (OG) domain. Using a powerful combination of small-angle X-ray scattering and single-molecule imaging, we demonstrate that pro-MMP-9 possesses an elongated structure with two terminal globular domains connected by an unstructured OG domain. Image analysis highlights the flexibility of the OG domain, implicating its role in the varied enzyme conformations and in facilitating independent movements of the terminal domains. This may endorse recognition, binding, and processing of substrates, ligands, as well as receptors and marks this domain as an additional target for the design of selective regulators.
ISSN: 0969-2126
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Immunobiology (Rega Institute)
* (joint) first author
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science