Crystal structure of the catalytic domain of MMP-16/MT3-MMP: Characterization of MT-MMP specific features

[en] Membrane-type matrix metalloproteinases (MT-MMPs) have attracted strong attention, because four of them can activate a key player in the tumor scenario, proMMP-2/progelatinase A. In addition to this indirect effect on the cellular environment, these MT-MMPs degrade extracellular matrix proteins, and their overproduction is associated with tumor growth. We have solved the structure of the catalytic domain (cd) of MT3-MMP/MMP-16 in complex with the hydroxamic acid inhibitor batimastat. CdMT3-MMP exhibits a classical MMP-fold with similarity to MT1-MMP. Nevertheless, it also shows unique properties such as a modified MT-specific loop and a closed S1' specificity pocket, which might help to design specific inhibitors. Some MT-MMP-specific features, derived from the crystal structures of MT-1-MMP determined previously and MT3-MMP, and revealed in recent mutagenesis experiments, explain the impaired interaction of the MT-MMPs with TIMP-1. Docking experiments with proMMP-2 show some exposed loops including the MT-loop of cdMT3-MMP involved in the interaction with the proMMP-2 prodomain in the activation encounter complex. This model might help to understand the experimentally proven importance of the MT-loop for the activation of proMMP-2. (C) 2003 Elsevier Ltd. All rights reserved.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Lang, R.

Braun, M.

Sounni, Nor Eddine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme

Frankenne, Francis

Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique

Bode, W.

Maskos, K.

Language :

English

Title :

Crystal structure of the catalytic domain of MMP-16/MT3-MMP: Characterization of MT-MMP specific features

Publication date :

06 February 2004

Journal title :

Journal of Molecular Biology

ISSN :

0022-2836

eISSN :

1089-8638

Publisher :

Academic Press, London, United Kingdom

Volume :

336

Issue :

Pages :

213-225

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 04 May 2009

Statistics

Number of views

183 (3 by ULiège)

Number of downloads

503 (0 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

McQuibban G.A., Gong J.H., Tam E.M., McCulloch C.A., Clark-Lewis I., Overall C.M. Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3. Science. 289:2000;1202-1206.
Noel A., Gilles C., Bajou K., Devy L., Kebers F., Lewalle J.M., et al. Emerging roles for proteinases in cancer. Invasion Metastasis. 17:1997;221-239.
Nagase H., Woessner J.F. Jr. Matrix metalloproteinases. J. Biol. Chem. 274:1999;21491-21494.
Stetler-Stevenson W.G. Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention. J. Clin. Invest. 103:1999;1237-1241.
McCawley L.J., Matrisian L.M. Matrix metalloproteinases: multifunctional contributors to tumor progression. Mol. Med. Today. 6:2000;149-156.
Sternlicht M.D., Werb Z. How matrix metalloproteinases regulate cell behavior. Annu. Rev. Cell. Dev. Biol. 17:2001;463-516.
Pei D. CA-MMP: a matrix metalloproteinase with a novel cysteine array, but without the classic cysteine switch. FEBS Letters. 457:1999;262-270.
Velasco G., Pendas A.M., Fueyo A., Knauper V., Murphy G., Lopez-Otin C. Cloning and characterization of human MMP-23, a new matrix metalloproteinase predominantly expressed in reproductive tissues and lacking conserved domains in other family members. J. Biol. Chem. 274:1999;4570-4576.
Itoh Y., Kajita M., Kinoh H., Mori H., Okada A., Seiki M. Membrane type 4 matrix metalloproteinase (MT4-MMP, MMP-17) is a glycosylphosphatidylinositol- anchored proteinase. J. Biol. Chem. 274:1999;34260-34266.
Kojima S., Itoh Y., Matsumoto S., Masuho Y., Seiki M. Membrane-type 6 matrix metalloproteinase (MT6-MMP, MMP-25) is the second glycosyl-phosphatidyl inositol (GPI)-anchored MMP. FEBS Letters. 480:2000;142-146.
Sato H., Takino T., Okada Y., Cao J., Shinagawa A., Yamamoto E., Seiki M. A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature. 370:1994;61-65.
Overall C. Molecular determinants of metalloproteinase substrate specificity: matrix metalloproteinase substrate binding domains, modules, and exosites. Mol. Biotechnol. 22:2002;51-86.
Deryugina E.I., Bourdon M.A., Jungwirth K., Smith J.W., Strongin A.Y. Functional activation of integrin alpha V beta 3 in tumor cells expressing membrane-type 1 matrix metalloproteinase. Int. J. Cancer. 86:2000;15-23.
Kajita M., Itoh Y., Chiba T., Mori H., Okada A., Kinoh H., Seiki M. Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. J. Cell Biol. 153:2001;893-904.
Strongin A.Y., Collier I., Bannikov G., Marmer B.L., Grant G.A., Goldberg G.I. Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of the activated form of the membrane metalloprotease. J. Biol. Chem. 270:1995;5331-5338.
Kinoshita T., Sato H., Takino T., Itoh M., Akizawa T., Seiki M. Processing of a precursor of 72-kilodalton type IV collagenase/gelatinase A by a recombinant membrane-type 1 matrix metalloproteinase. Cancer Res. 56:1996;2535-2538.
Will H., Atkinson S.J., Butler G.S., Smith B., Murphy G. The soluble catalytic domain of membrane type 1 matrix metalloproteinase cleaves the propeptide of progelatinase A and initiates autoproteolytic activation. Regulation by TIMP-2 and TIMP-3. J. Biol. Chem. 271:1996;17119-17123.
Butler G.S., Hutton M., Wattam B.A., Williamson R.A., Knauper V., Willenbrock F., Murphy G. The specificity of TIMP-2 for matrix metalloproteinases can be modified by single amino acid mutations. J. Biol. Chem. 274:1999;20391-20396.
Butler G., Will H., Atkinson S.J., Murphy G. Membrane-type-2 matrix metalloproteinase can initiate the processing of progelatinase A and is regulated by the tissue inhibitors of metalloproteinases. Eur. J. Biochem. 244:1997;653-657.
Kolkenbrock H., Hecker-Kia A., Orgel D., Ulbrich N., Will H. Activation of progelatinase A and progelatinase A/TIMP-2 complex by membrane type 2-matrix metalloproteinase. Biol. Chem. 378:1997;71-76.
Llano E., Pendas A.M., Freije J.P., Nakano A., Knauper V., Murphy G., Lopez-Otin C. Identification and characterization of human MT5-MMP, a new membrane-bound activator of progelatinase A overexpressed in brain tumors. Cancer Res. 59:1999;2570-2576.
Takino T., Sato H., Shinagawa A., Seiki M. Identification of the second membrane-type matrix metalloproteinase (MT-MMP-2) gene from a human placenta cDNA library. MT-MMPs form a unique membrane-type subclass in the MMP family. J. Biol. Chem. 270:1995;23013-23020.
Pei D. Identification and characterization of the fifth membrane-type matrix metalloproteinase MT5-MMP. J. Biol. Chem. 274:1999;8925-8932.
Morrison C.J., Butler G.S., Bigg H.F., Roberts C.R., Soloway P.D., Overall C.M. Cellular activation of MMP-2 (gelatinase A) by MT2-MMP occurs via a TIMP-2-independent pathway. J. Biol. Chem. 276:2001;47402-474010.
Fernandez-Catalan C., Bode W., Huber R., Turk D., Calvete J.J., Lichte A., et al. Crystal structure of the complex formed by the membrane type 1-matrix metalloproteinase with the tissue inhibitor of metalloproteinases-2, the soluble progelatinase A receptor. EMBO J. 17:1998;5238-5248.
English W.R., Holtz B., Vogt G., Knauper V., Murphy G. Characterization of the role of the MT-loop: an eight-amino acid insertion specific to progelatinase A (MMP2) activating membrane-type matrix metalloproteinases. J. Biol. Chem. 276:2001;42018-42026.
English W.R., Puente X.S., Freije J.M., Knauper V., Amour A., Merryweather A., et al. Membrane type 4 matrix metalloproteinase (MMP17) has tumor necrosis factor-alpha convertase activity but does not activate pro-MMP2. J. Biol. Chem. 275:2000;14046-14055.
Velasco G., Cal S., Merlos-Suarez A., Ferrando A.A., Alvarez S., Nakano A., et al. Human MT6-matrix metalloproteinase: identification, progelatinase A activation, and expression in brain tumors. Cancer Res. 60:2000;877-882.
Kojima S., Itoh Y., Matsumoto S., Masuho Y., Seiki M. Membrane-type 6 matrix metalloproteinase (MT6-MMP, MMP-25) is the second glycosyl-phosphatidyl inositol (GPI)-anchored MMP. FEBS Letters. 480:2000;142-146.
Zhou Z., Apte S.S., Soininen R., Cao R., Baaklini G.Y., Rauser R.W., et al. Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I. Proc. Natl Acad. Sci. USA. 97:2000;4052-4057.
Holmbeck K., Bianco P., Caterina J., Yamada S., Kromer M., Kuznetsov S.A., et al. MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell. 99:1999;81-92.
Yoshiyama Y., Sato H., Seiki M., Shinagawa A., Takahashi M., Yamada T. Expression of the membrane-type 3 matrix metalloproteinase (MT3-MMP) in human brain tissues. Acta Neuropathol. (Berl.). 96:1998;347-350.
Nakada M., Nakamura H., Ikeda E., Fujimoto N., Yamashita J., Sato H., et al. Expression and tissue localization of membrane-type 1, 2, and 3 matrix metalloproteinases in human astrocytic tumors. Am. J. Pathol. 154:1999;417-428.
Kitagawa Y., Kunimi K., Uchibayashi T., Sato H., Namiki M. Expression of messenger RNAs for membrane-type 1, 2, and 3 matrix metalloproteinases in human renal cell carcinomas. J. Urol. 162:1999;905-909.
Ueno H., Nakamura H., Inoue M., Imai K., Noguchi M., Sato H., et al. Expression and tissue localization of membrane-types 1, 2, and 3 matrix metalloproteinases in human invasive breast carcinomas. Cancer Res. 57:1997;2055-2060.
Iida J., Pei D., Kang T., Simpson M.A., Herlyn M., Furcht L.T., McCarthy J.B. Melanoma chondroitin sulfate proteoglycan regulates matrix metalloprotease-dependent human melanoma invasion into type I collagen. J. Biol. Chem. 276:2001;18786-18794.
Kang T., Yi J., Yang W., Wang X., Jiang A., Pei D. Functional characterization of MT3-MMP in transfected MDCK cells: progelatinase A activation and tubulogenesis in 3-D collagen lattice. FASEB J. 14:2000;2559-2568.
Shofuda K., Yasumitsu H., Nishihashi A., Miki K., Miyazaki K. Expression of three membrane-type matrix metalloproteinases (MT-MMPs) in rat vascular smooth muscle cells and characterization of MT3-MMPs with and without transmembrane domain. J. Biol. Chem. 272:1997;9749-9754.
Matsumoto S., Katoh M., Saito S., Watanabe T., Masuho Y. Identification of soluble type of membrane-type matrix metalloproteinase-3 formed by alternatively spliced mRNA. Biochim. Biophys. Acta. 1354:1997;159-170.
Shimada T., Nakamura H., Ohuchi E., Fujii Y., Murakami Y., Sato H., et al. Characterization of a truncated recombinant form of human membrane type 3 matrix metalloproteinase. Eur. J. Biochem. 262:1999;907-914.
Reinemer P., Grams F., Huber R., Kleine T., Schnierer S., Pieper M., et al. Structural implications for the role of the N terminus in the, superactivation' of collagenases. A crystallographic study. FEBS Letters. 338:1994;227-233.
Chung L., Shimakawa K., Dinakarpandian D., Grams F., Firlds G.B., Nagase H. Identification of the (183)RWTNNFREY(191) region as a critical segment of matrix metalloprotease 1 for the expression of collagenolytic activity. J. Biol. Chem. 275:2000;29610-29617.
Bode W., Gomis-Ruth F.X., Stocker W. Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the metzincins. FEBS Letters. 331:1993;134-140.
Bode W., Reinemer P., Huber R., Kleine T., Schnierer S., Tschesche H. The X-ray crystal structure of the catalytic domain of human neutrophil collagenase inhibited by a substrate analogue reveals the essentials for catalysis and specificity. EMBO J. 13:1994;1263-1269.
Lovejoy B., Cleasby A., Hassell A.M., Longley K., Luther M.A., Weigl D., et al. Structure of the catalytic domain of fibroblast collagenase complexed with an inhibitor. Science. 263:1994;375-377.
Kridel S.J., Sawai H., Ratnikov B.I., Chan E.I., Li W., Godzik A., Strongin A.Y., et al. A unique substrate binding mode discriminates membrane type-1 matrix metalloproteinase from other matrix metalloproteinases. J. Biol. Chem. 277:2002;23788-23793.
Lovejoy B., Welch A.R., Carr S., Luong C., Broka C., Hendricks R.T., et al. Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors. Nat. Struct. Biol. 6:1999;217-221.
Grams F., Crimmin M., Hinnes L., Huxley P., Pieper M., Tschesche H., Bode W. Structure determination and analysis of human neutrophil collagenase complexed with a hydroxamate inhibitor. Biochemistry. 34:1995;14012-14020.
Tanaka M., Sato H., Takino T., Iwata K., Inoue M., Seiki M. Isolation of a mouse MT2-MMP gene from a lung cDNA library and identification of its product. FEBS Letters. 402:1997;219-222.
Miyamori H., Takino T., Seiki M., Sato H. Human membrane type-2 matrix metalloproteinase is defective in cell-associated activation of progelatinase A. Biochem. Biophys. Res. Commun. 267:2000;796-800.
Morgunova E., Tuuttila A., Bergmann U., Isupov M., Lindqvist Y., Schneider G., Tryggvason K. Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed. Science. 284:1999;1667-1670.
Strongin A.Y., Marmer B.L., Grant G.A., Goldberg G.I. Plasma membrane-dependent activation of the 72-kDa type IV collagenase is prevented by complex formation with TIMP-2. J. Biol. Chem. 268:1993;14033-14039.
Atkinson S.J., Crabbe T., Cowell S., Ward R.V., Butler M.J., Sato H., et al. Intermolecular autolytic cleavage can contribute to the activation of progelatinase A by cell membranes. J. Biol. Chem. 270:1995;30479-30485.
Morgunova E., Tuuttila A., Bergmann U., Tryggvason K. Structural insights into the complex formation of latent matrix metalloproteinase 2 with tissue inhibitor of metalloproteinase 2. Proc. Natl Acad. Sci. USA. 99:2002;7414-7419.
Grams F., Reinemer P., Powers J.C., Kleine T., Pieper M., Tschesche H., Huber R., Bode W. X-ray structures of human neutrophil collagenase complexed with peptide hydroxamate and peptide thiol inhibitors. Implications for substrate binding and rational drug design. Eur. J. Biochem. 228:1995;830-841.
Bode W., Maskos K. Structural basis of the matrix metalloproteinases and their physiological inhibitors, the tissue inhibitors of metalloproteinases. Biol. Chem. 384:2003;863-872.
Lang, R. (2001). Röntgenstrukturanalyse der katalytischen Domänen von Makrophagen Elastase (MMP-12), MT3-MMP (MMP-16) und dem Komplex aus Kollagenase-3 (MMP-13) mit TIMP-2. Dissertation, München.
Knauper V., Bailey L., Worley J.R., Soloway P., Patterson M.L., Murphy G. Cellular activation of proMMP-13 by MT1-MMP depends on the C-terminal domain of MMP-13. FEBS Letters. 532:2002;127-130.
Gomis-Ruth F.X., Maskos K., Betz M., Bergner A., Huber R., Suzuki K., et al. Mechanism of inhibition of the human matrix metalloproteinase stromelysin-1 by TIMP-1. Nature. 389:1997;77-81.
Lee M.H., Rapti M., Murphy G. Unveiling the surface epitopes that render tissue inhibitor of metalloproteinase (TIMP)-1 inactive against membrane type 1-matrix metalloproteinase (MT1-MMP). J. Biol. Chem. 278:2003;40224-40230.
L'Hoir C., Renard A., Martial J.A. Expression in Escherichia coli of two mutated genes encoding the cholera toxin B subunit. Gene. 89:1990;47-52.
Noel A., Santavicca M., Stoll I., L'Hoir C., Staub A., Murphy G., et al. Identification of structural determinants controlling human and mouse stromelysin-3 proteolytic activities. J. Biol. Chem. 270:1995;22866-22872.
Amour A., Slocombe P.M., Webster A., Butler M., Knight C.G., Smith B.J., et al. TNF-alpha converting enzyme (TACE) is inhibited by TIMP-3. FEBS Letters. 435:1998;39-44.
Otwinowski Z., Minor W. Processing of X-ray diffraction data collected in oscillations mode. Methods Enzymol. 276:1997;307-326.
Navaza J. AMoRe: an automated package for molecular replacement. Acta Crystallog. A50:1994;157-163.
Brünger A.T. X-PLOR Version 3.1. A system for X-ray crystallography and NMR. 1992;Yale University Press, New Haven, CT.
Engh R.A., Huber R. Accurate bond and angle parameters for X-ray protein structure refinement. Acta Crystallog. sect. D. 4:(1):1991;392-400.
Brünger A.T., Adams P.D., Clore G.M., Delano W.L., Gros P., Grosse-Kunstleve R.W., et al. Crystallography and NMR systems (CNS): a new software system for macromolecular structure determination. Acta Crystallog. sect. D. 54:1998;905-921.
Jones T.A., Zou J.Y., Cowan S.W., Kjelgaard M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallog. A47:1991;110-119.
Turk, D. (1992). Weiterentwicklung eines Programms für Molekülgraphik und Elektronendichte-Manipulation und seine Anwendung auf verschiedene Protein-Strukturaufklärungen. Ph.D. thesis, München.
Murshudov G.N., Lebedev A., Vagin A.A., Wilson K.S., Dodson E.J. Efficient anisotropic refinement of macromolecular structures using FFT. Acta Crystallog. sect. D. 55:1999;247-255.
Laskowski R.A., MacArthur M.W., Moss D.S., Thornton J.M. PROCHECK: a program to check the stereochemical quality of protein structures. J. Appl. Crystallog. 26:1993;283-291.
Esnouf R.M. An extensively modified version of MolScript that includes greatly enhanced coloring capabilities. J. Mol. Graph. Model. 15:1997;132-134.
Merritt E.A., Murphy M.E.P. Raster3D version 2.0. A program for photorealistic molecular graphics. Acta Crystallog. sect. D. 50:1994;869-873.
Guex N., Peitsch M.C. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis. 18:1997;2714-2723.