TY - JOUR
T1 - Insights into the Structure and Domain Flexibility of Full-Length Pro-Matrix Metalloproteinase-9/Gelatinase B
AU - Rosenblum, Gabriel
AU - Van den Steen, Philippe E.
AU - Cohen, Sidney R.
AU - Grossmann, J. Günter
AU - Frenkel, Jessica
AU - Sertchook, Rotem
AU - Slack, Nelle
AU - Strange, Richard W.
AU - Opdenakker, Ghislain
AU - Sagi, Irit
PY - 2007/10/16
Y1 - 2007/10/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=35148837731&partnerID=8YFLogxK
U2 - 10.1016/j.str.2007.07.019
DO - 10.1016/j.str.2007.07.019
M3 - Article
SN - 0969-2126
VL - 15
SP - 1227
EP - 1236
JO - Structure
JF - Structure
IS - 10
ER -