Skip to main content
NCBI home page
Biophysical Journal logoLink to Biophysical Journal
. 2001 Oct;81(4):2370–2377. doi: 10.1016/S0006-3495(01)75883-3

Substrate recognition by gelatinase A: the C-terminal domain facilitates surface diffusion.

I E Collier 1, S Saffarian 1, B L Marmer 1, E L Elson 1, G Goldberg 1
PMCID: PMC1301707  PMID: 11566806

Abstract

An investigation of gelatinase A binding to gelatin produced results that are inconsistent with a traditional bimolecular Michaelis-Menten formalism but are effectively accounted for by a power law characteristic of fractal kinetics. The main reason for this inconsistency is that the bulk of the gelatinase A binding depends on its ability to diffuse laterally on the gelatin surface. Most interestingly, we show that the anomalous lateral diffusion and, consequently, the binding to gelatin is greatly facilitated by the C-terminal hemopexin-like domain of the enzyme whereas the specificity of binding resides with the fibronectin-like gelatin-binding domain.

Full Text

The Full Text of this article is available as a PDF (308.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Axelrod D., Koppel D. E., Schlessinger J., Elson E., Webb W. W. Mobility measurement by analysis of fluorescence photobleaching recovery kinetics. Biophys J. 1976 Sep;16(9):1055–1069. doi: 10.1016/S0006-3495(76)85755-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Braithwaite GJ, Luckham PF, Howe AM. Study of a Solvated Adsorbed Gelatin Layer Using a Modified Force Microscope. J Colloid Interface Sci. 1999 May 15;213(2):525–545. doi: 10.1006/jcis.1999.6134. [DOI] [PubMed] [Google Scholar]
  3. Brooks P. C., Strömblad S., Sanders L. C., von Schalscha T. L., Aimes R. T., Stetler-Stevenson W. G., Quigley J. P., Cheresh D. A. Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Cell. 1996 May 31;85(5):683–693. doi: 10.1016/s0092-8674(00)81235-0. [DOI] [PubMed] [Google Scholar]
  4. Brooks P. C., Strömblad S., Sanders L. C., von Schalscha T. L., Aimes R. T., Stetler-Stevenson W. G., Quigley J. P., Cheresh D. A. Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3. Cell. 1996 May 31;85(5):683–693. doi: 10.1016/s0092-8674(00)81235-0. [DOI] [PubMed] [Google Scholar]
  5. Butler G. S., Butler M. J., Atkinson S. J., Will H., Tamura T., Schade van Westrum S., Crabbe T., Clements J., d'Ortho M. P., Murphy G. The TIMP2 membrane type 1 metalloproteinase "receptor" regulates the concentration and efficient activation of progelatinase A. A kinetic study. J Biol Chem. 1998 Jan 9;273(2):871–880. doi: 10.1074/jbc.273.2.871. [DOI] [PubMed] [Google Scholar]
  6. Chiquet M. Regulation of extracellular matrix gene expression by mechanical stress. Matrix Biol. 1999 Oct;18(5):417–426. doi: 10.1016/s0945-053x(99)00039-6. [DOI] [PubMed] [Google Scholar]
  7. Collier I. E., Krasnov P. A., Strongin A. Y., Birkedal-Hansen H., Goldberg G. I. Alanine scanning mutagenesis and functional analysis of the fibronectin-like collagen-binding domain from human 92-kDa type IV collagenase. J Biol Chem. 1992 Apr 5;267(10):6776–6781. [PubMed] [Google Scholar]
  8. Collier I. E., Wilhelm S. M., Eisen A. Z., Marmer B. L., Grant G. A., Seltzer J. L., Kronberger A., He C. S., Bauer E. A., Goldberg G. I. H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen. J Biol Chem. 1988 May 15;263(14):6579–6587. [PubMed] [Google Scholar]
  9. Damsky C. H., Moursi A., Zhou Y., Fisher S. J., Globus R. K. The solid state environment orchestrates embryonic development and tissue remodeling. Kidney Int. 1997 May;51(5):1427–1433. doi: 10.1038/ki.1997.195. [DOI] [PubMed] [Google Scholar]
  10. 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. 2000 Apr 1;86(1):15–23. doi: 10.1002/(sici)1097-0215(20000401)86:1<15::aid-ijc3>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  11. Deryugina E. I., Bourdon M. A., Reisfeld R. A., Strongin A. Remodeling of collagen matrix by human tumor cells requires activation and cell surface association of matrix metalloproteinase-2. Cancer Res. 1998 Aug 15;58(16):3743–3750. [PubMed] [Google Scholar]
  12. Feder T. J., Brust-Mascher I., Slattery J. P., Baird B., Webb W. W. Constrained diffusion or immobile fraction on cell surfaces: a new interpretation. Biophys J. 1996 Jun;70(6):2767–2773. doi: 10.1016/S0006-3495(96)79846-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fridman R., Fuerst T. R., Bird R. E., Hoyhtya M., Oelkuct M., Kraus S., Komarek D., Liotta L. A., Berman M. L., Stetler-Stevenson W. G. Domain structure of human 72-kDa gelatinase/type IV collagenase. Characterization of proteolytic activity and identification of the tissue inhibitor of metalloproteinase-2 (TIMP-2) binding regions. J Biol Chem. 1992 Aug 5;267(22):15398–15405. [PubMed] [Google Scholar]
  14. Friedl P., Bröcker E. B. The biology of cell locomotion within three-dimensional extracellular matrix. Cell Mol Life Sci. 2000 Jan 20;57(1):41–64. doi: 10.1007/s000180050498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Frisch S. M., Reich R., Collier I. E., Genrich L. T., Martin G., Goldberg G. I. Adenovirus E1A represses protease gene expression and inhibits metastasis of human tumor cells. Oncogene. 1990 Jan;5(1):75–83. [PubMed] [Google Scholar]
  16. Goldberg G. I., Marmer B. L., Grant G. A., Eisen A. Z., Wilhelm S., He C. S. Human 72-kilodalton type IV collagenase forms a complex with a tissue inhibitor of metalloproteases designated TIMP-2. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8207–8211. doi: 10.1073/pnas.86.21.8207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Goldberg G. I., Strongin A., Collier I. E., Genrich L. T., Marmer B. L. Interaction of 92-kDa type IV collagenase with the tissue inhibitor of metalloproteinases prevents dimerization, complex formation with interstitial collagenase, and activation of the proenzyme with stromelysin. J Biol Chem. 1992 Mar 5;267(7):4583–4591. [PubMed] [Google Scholar]
  18. Karsenty G. The genetic transformation of bone biology. Genes Dev. 1999 Dec 1;13(23):3037–3051. doi: 10.1101/gad.13.23.3037. [DOI] [PubMed] [Google Scholar]
  19. Kinoshita T., Sato H., Okada A., Ohuchi E., Imai K., Okada Y., Seiki M. TIMP-2 promotes activation of progelatinase A by membrane-type 1 matrix metalloproteinase immobilized on agarose beads. J Biol Chem. 1998 Jun 26;273(26):16098–16103. doi: 10.1074/jbc.273.26.16098. [DOI] [PubMed] [Google Scholar]
  20. Kleiner D. E., Stetler-Stevenson W. G. Matrix metalloproteinases and metastasis. Cancer Chemother Pharmacol. 1999;43 (Suppl):S42–S51. doi: 10.1007/s002800051097. [DOI] [PubMed] [Google Scholar]
  21. Knäuper V., Cowell S., Smith B., López-Otin C., O'Shea M., Morris H., Zardi L., Murphy G. The role of the C-terminal domain of human collagenase-3 (MMP-13) in the activation of procollagenase-3, substrate specificity, and tissue inhibitor of metalloproteinase interaction. J Biol Chem. 1997 Mar 21;272(12):7608–7616. doi: 10.1074/jbc.272.12.7608. [DOI] [PubMed] [Google Scholar]
  22. 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. 1997 Feb;378(2):71–76. doi: 10.1515/bchm.1997.378.2.71. [DOI] [PubMed] [Google Scholar]
  23. Kopelman R. Fractal reaction kinetics. Science. 1988 Sep 23;241(4873):1620–1626. doi: 10.1126/science.241.4873.1620. [DOI] [PubMed] [Google Scholar]
  24. Massova I., Kotra L. P., Fridman R., Mobashery S. Matrix metalloproteinases: structures, evolution, and diversification. FASEB J. 1998 Sep;12(12):1075–1095. [PubMed] [Google Scholar]
  25. 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. 1999 Jun 4;284(5420):1667–1670. doi: 10.1126/science.284.5420.1667. [DOI] [PubMed] [Google Scholar]
  26. Murphy G., Knäuper V. Relating matrix metalloproteinase structure to function: why the "hemopexin" domain? Matrix Biol. 1997 Mar;15(8-9):511–518. doi: 10.1016/s0945-053x(97)90025-1. [DOI] [PubMed] [Google Scholar]
  27. Norrby K. Angiogenesis: new aspects relating to its initiation and control. APMIS. 1997 Jun;105(6):417–437. doi: 10.1111/j.1699-0463.1997.tb00590.x. [DOI] [PubMed] [Google Scholar]
  28. Olson M. W., Gervasi D. C., Mobashery S., Fridman R. Kinetic analysis of the binding of human matrix metalloproteinase-2 and -9 to tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. J Biol Chem. 1997 Nov 21;272(47):29975–29983. doi: 10.1074/jbc.272.47.29975. [DOI] [PubMed] [Google Scholar]
  29. Petersen N. O., Elson E. L. Measurements of diffusion and chemical kinetics by fluorescence photobleaching recovery and fluorescence correlation spectroscopy. Methods Enzymol. 1986;130:454–484. doi: 10.1016/0076-6879(86)30021-1. [DOI] [PubMed] [Google Scholar]
  30. 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. 1995 Mar 10;270(10):5331–5338. doi: 10.1074/jbc.270.10.5331. [DOI] [PubMed] [Google Scholar]
  31. 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. 1993 Jul 5;268(19):14033–14039. [PubMed] [Google Scholar]
  32. Trojanowska M., LeRoy E. C., Eckes B., Krieg T. Pathogenesis of fibrosis: type 1 collagen and the skin. J Mol Med (Berl) 1998 Mar;76(3-4):266–274. doi: 10.1007/s001090050216. [DOI] [PubMed] [Google Scholar]
  33. Vu T. H., Werb Z. Matrix metalloproteinases: effectors of development and normal physiology. Genes Dev. 2000 Sep 1;14(17):2123–2133. doi: 10.1101/gad.815400. [DOI] [PubMed] [Google Scholar]
  34. Werb Z., Chin J. R. Extracellular matrix remodeling during morphogenesis. Ann N Y Acad Sci. 1998 Oct 23;857:110–118. doi: 10.1111/j.1749-6632.1998.tb10111.x. [DOI] [PubMed] [Google Scholar]
  35. Wilhelm S. M., Collier I. E., Kronberger A., Eisen A. Z., Marmer B. L., Grant G. A., Bauer E. A., Goldberg G. I. Human skin fibroblast stromelysin: structure, glycosylation, substrate specificity, and differential expression in normal and tumorigenic cells. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6725–6729. doi: 10.1073/pnas.84.19.6725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wilhelm S. M., Collier I. E., Marmer B. L., Eisen A. Z., Grant G. A., Goldberg G. I. SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages. J Biol Chem. 1989 Oct 15;264(29):17213–17221. [PubMed] [Google Scholar]
  37. Woodhouse E. C., Chuaqui R. F., Liotta L. A. General mechanisms of metastasis. Cancer. 1997 Oct 15;80(8 Suppl):1529–1537. doi: 10.1002/(sici)1097-0142(19971015)80:8+<1529::aid-cncr2>3.3.co;2-#. [DOI] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES