scholarly journals Membrane type 1 matrix metalloproteinase (MT1-MMP) cleaves the recombinant aggrecan substrate rAgg1mut at the ‘aggrecanase’ and the MMP sites

1998 ◽  
Vol 333 (1) ◽  
pp. 159-165 ◽  
Author(s):  
Frank H. BÜTTNER ◽  
Clare E. HUGHES ◽  
Daniel MARGERIE ◽  
Andrea LICHTE ◽  
Harald TSCHESCHE ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Catalytic Domain ◽  
Human Articular Cartilage ◽  
Recombinant Enzymes ◽  
Recombinant Product ◽  
Weak Activity ◽  
Membrane Type

The recent detection of membrane type 1 matrix metalloproteinase (MT1-MMP) expression in human articular cartilage [Büttner, Chubinskaya, Margerie, Huch, Flechtenmacher, Cole, Kuettner, and Bartnik (1997) Arthritis Rheum. 40, 704–709] prompted our investigation of MT1-MMP's catabolic activity within the interglobular domain of aggrecan. For these studies we used rAgg1mut, a mutated form of the recombinant fusion protein (rAgg1) that has been used as a substrate to monitor ‘aggrecanase ’ catabolism in vitro [Hughes, Büttner, Eidenmüller, Caterson and Bartnik (1997) J. Biol. Chem. 272, 20269–20274]. The rAgg1 was mutated (G332 to A) to avoid the generation of a splice variant seen with the original genetic construct, which gave rise to heterogeneous glycoprotein products. This mutation yielded a homogeneous recombinant product. Studies in vitro with retinoic acid-stimulated rat chondrosarcoma cells indicated that the rAgg1mut substrate was cleaved at the ‘aggrecanase ’ site equivalent to Glu373-Ala374 (human aggrecan sequence enumeration) in its interglobular domain sequence segment. The differential catabolic activities of the recombinant catalytic domain (cd) of MT1-MMP and matrix metalloproteinases (MMPs) 3 and 8 were then compared by using this rAgg1mut as a substrate. Coomassie staining of rAgg1mut catabolites separated by SDS/PAGE showed similar patterns of degradation with all three recombinant enzymes. However, comparative immunodetection analysis, with neoepitope antibodies BC-3 (anti-ARGS …) and BC-14 (anti-FFGV …) to distinguish between ‘aggrecanase ’ and MMP-generated catabolites, indicated that the catalytic domain of MT1-MMP exhibited strong ‘aggrecanase ’ activity, cdMMP-8 weak activity and cdMMP-3 no activity. In contrast, cdMMP-3 and cdMMP-8 led to strongly BC-14-reactive catabolic fragments, whereas cdMT1-MMP resulted in weak BC-14 reactivity. N-terminal sequence analyses of the catabolites confirmed these results and also identified other potential minor cleavage sites within the interglobular domain of aggrecan. These results indicate that MT1-MMP is yet another candidate for ‘aggrecanase ’ activity in vivo.

scholarly journals Molecular Dissection of the Structural Machinery Underlying the Tissue-invasive Activity of Membrane Type-1 Matrix Metalloproteinase

2008 ◽  
Vol 19 (8) ◽  
pp. 3221-3233 ◽  
Author(s):  
Xiao-Yan Li ◽  
Ichiro Ota ◽  
Ikuo Yana ◽  
Farideh Sabeh ◽  
Stephen J. Weiss
Keyword(s):  
Matrix Metalloproteinase ◽  
Type I Collagen ◽  
Cell Function ◽  
Catalytic Domain ◽  
Transmembrane Domain ◽  
Type I ◽  
Cell Trafficking ◽  
Membrane Type

Membrane type-1 matrix metalloproteinase (MT1-MMP) drives cell invasion through three-dimensional (3-D) extracellular matrix (ECM) barriers dominated by type I collagen or fibrin. Based largely on analyses of its impact on cell function under two-dimensional culture conditions, MT1-MMP is categorized as a multifunctional molecule with 1) a structurally distinct, N-terminal catalytic domain; 2) a C-terminal hemopexin domain that regulates substrate recognition as well as conformation; and 3) a type I transmembrane domain whose cytosolic tail controls protease trafficking and signaling cascades. The MT1-MMP domains that subserve cell trafficking through 3-D ECM barriers in vitro or in vivo, however, remain largely undefined. Herein, we demonstrate that collagen-invasive activity is not confined strictly to the catalytic, hemopexin, transmembrane, or cytosolic domain sequences of MT1-MMP. Indeed, even a secreted collagenase supports invasion when tethered to the cell surface in the absence of the MT1-MMP hemopexin, transmembrane, and cytosolic tail domains. By contrast, the ability of MT1-MMP to support fibrin-invasive activity diverges from collagenolytic potential, and alternatively, it requires the specific participation of MT-MMP catalytic and hemopexin domains. Hence, the tissue-invasive properties of MT1-MMP are unexpectedly embedded within distinct, but parsimonious, sequences that serve to tether the requisite matrix-degradative activity to the surface of migrating cells.

Immunohistochemical localization of membrane type 1-matrix metalloproteinase (MT1-MMP) in osteoclasts in vivo

2001 ◽  
Vol 33 (5) ◽  
pp. 478-482 ◽  
Author(s):  
K. Irie, ◽  
E. Tsuruga, ◽  
Y. Sakakura, ◽  
T. Muto, ◽  
T. Yajima
Keyword(s):  
Matrix Metalloproteinase ◽  
Immunohistochemical Localization ◽  
Membrane Type

Expression OF membrane type 1 matrix metalloproteinase in human articular cartilage

1997 ◽  
Vol 40 (4) ◽  
pp. 704-709 ◽  
Author(s):  
Frank H. Büttner ◽  
Susan Chubinskaya ◽  
Daniel Margerie ◽  
Klaus Huch ◽  
Johannes Flechtenmacher ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Matrix Metalloproteinase ◽  
Human Articular Cartilage ◽  
Membrane Type

scholarly journals The Soluble Catalytic Domain of Membrane Type 1 Matrix Metalloproteinase Cleaves the Propeptide of Progelatinase A and Initiates Autoproteolytic Activation

1996 ◽  
Vol 271 (29) ◽  
pp. 17119-17123 ◽  
Author(s):  
Horst Will ◽  
Susan J. Atkinson ◽  
Georgina S. Butler ◽  
Bryan Smith ◽  
Gillian Murphy
Keyword(s):  
Matrix Metalloproteinase ◽  
Catalytic Domain ◽  
Membrane Type

scholarly journals In Vitro Efficacy of a Sterically Stabilized Immunoliposomes Targeted to Membrane Type 1 Matrix Metalloproteinase (MT1-MMP)

2007 ◽  
Vol 30 (5) ◽  
pp. 972-978 ◽  
Author(s):  
Kazutaka Atobe ◽  
Tatsuhiro Ishida ◽  
Emi Ishida ◽  
Kouichi Hashimoto ◽  
Hideo Kobayashi ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Membrane Type

scholarly journals Membrane type-1 matrix metalloproteinase is induced following cyclic compression of in vitro grown bovine chondrocytes

2007 ◽  
Vol 15 (11) ◽  
pp. 1301-1310 ◽  
Author(s):  
J.N.A. De Croos ◽  
B. Jang ◽  
S.S. Dhaliwal ◽  
M.D. Grynpas ◽  
R.M. Pilliar ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Cyclic Compression ◽  
Membrane Type

scholarly journals Membrane interactions with membrane type 1 matrix metalloproteinase

2018 ◽  
Author(s):  
◽  
Tara Marcink
Keyword(s):  
Cell Surface ◽  
Matrix Metalloproteinase ◽  
Catalytic Domain ◽  
Membrane Surface ◽  
Membrane Binding ◽  
Tumor Cell Migration ◽  
Peripheral Protein ◽  
Membrane Type ◽  
Dynamics Simulations

Membrane type 1 matrix metalloproteinase (MT1-MMP) is essential to a myriad of extracellular activities including tumor cell migration and angiogenesis. At the cell surface, MT1-MMP is a major factor in the proteolysis of receptors, growth factors, and collagen. MT1-MMP extracellular domains bind the cell surface which can be influential in bringing these complexes together. This study uses new techniques to uncover the interactions between MT1-MMP and the cell surface. Described here is the development of techniques in protein and lipid preparations, NMR data acquisition, and structure determination by molecular dynamics simulations. Through these methods, the HPX domain was shown to bind nanodiscs by opposing tips of blade II and blade IV. The protruding part of these tips contain an EPGYPK sequence that are seen dipping into the membrane surface making contact with the lipid head groups. Blade IV membrane binding allows collagen to bind unhindered. Both blade II and blade IV membrane binding structures are shown to be favorable for homodimerization without disruption of the collagen binding site. The catalytic domain is shown to at least transiently bind membranes. This study then hypothesizes and discusses how these interactions impact both future peripheral protein membrane interaction studies and uncover similarities between the MMP family.

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