Membrane Metalloendopeptidases in Immune Function and Disease

  • Judith S. Bond
  • Weiping Jiang
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 421)


The enzymes that compose the ‘Metallopeptidases’ are a diverse group1. Forty-seven distinct evolutionary families of metallopeptidases have been identified in the last eight years; more than for any other protease classes, i.e., the serine/threonine, cysteine, or aspartic classes of proteases (see the Peptidase World Wide Web sites: and htpp:// In 1987, the primary amino acid sequence of very few metallopeptidases and of only one mammalian metalloendopeptidase (human fibroblast collagenase) were known, and the 3-dimensional structures of very few metallopeptidases (thermolysin, carboxypeptidase A and B) were solved2. 3. Now hundreds of sequences of members of this Class are known, and many x-ray structures have been determined to high resolution (see, for example, reference 4). Thus our information about this class is expanding rapidly.


Major Histocompatibility Complex Myelin Basic Protein Snake Venom Primary Amino Acid Sequence Major Histocompatibility Complex Genotypes42 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Rawlings ND, and Barrett AJ (1995) Evolutionary families of metallopeptidases. Methods Enzymol 248: 183–228PubMedCrossRefGoogle Scholar
  2. 2.
    Bond.IS, and Butler PE (1987) Intracellular proteases. Annu Rev Biochem 56: 333–364CrossRefGoogle Scholar
  3. 3.
    Bond JS, and Beynon RJ (1987) Proteolysis and physiological regulation. Molec Aspects Med 9: 173–287CrossRefGoogle Scholar
  4. 4.
    Stöcker W. Grams F, Baumann U, Reinemer P, Gomis-Ruth EX, McKay DB. and Bode W (1995) The metzincins–Topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagcnases) define a superfamily of zinc-peptidases. Protein Sci 4: 823–840PubMedGoogle Scholar
  5. 5.
    Bouvier J. Schneider P, and Etges R (1995) Leishmanolysin: Surface metalloproteinase of Leishmania. Methods Enzymol 248: 614–633Google Scholar
  6. 6.
    Ehlers MRW, and Riordan JF (1991)Membrane prtoeins with soluble counterparts: Role of proteolysis in the release of transmembrane proteins. Biochemistry 30: 10065–10074Google Scholar
  7. 7.
    Massagué J, and Pandiella A (1993) Membrane-anchored growth factors. Annu Rev Biochem 62: 515–541PubMedCrossRefGoogle Scholar
  8. 8.
    Rose-John S, and Heinrich PC (1994) Soluble receptors for cytokines and growth factors: Generation and biological function. Biochem J 300: 281–290PubMedGoogle Scholar
  9. 9.
    Beaumont A, Fournie-Zaluski MC, and Roques BP (1996) Neutral endopeptidase-24.I I: structure and design and clinical use of inhibitors. In: Zinc Metalloproteases in Health and Disease. NM Hooper, ed. Taylor and Francis Ltd, London, pp. 105–129Google Scholar
  10. 10.
    Li C, and Hersh LB (1995) Neprilysin: Assay methods, purification, and characterization. Methods Enzymol 248: 253–263PubMedCrossRefGoogle Scholar
  11. 11.
    Turner AJ, and Tanzawa K (1996) Endothelin converting enzyme: structure and localization. In: Zinc Metalloproteases in Health and Disease, NM Hooper, ed, Taylor and Francis Ltd, London, pp. 311–331Google Scholar
  12. 12.
    Wolz RL, and Bond JS (1995) Meprins A and B. Methods Enzymol 248: 325–345PubMedCrossRefGoogle Scholar
  13. 13.
    Marchand P, and Bond JS (1996) Structure and membrane association of mouse and rat meprins. In: Intracelluar Protein Catabolism, K Suzuki and JS Bond, eds, Plenum Press, New York, pp. 13–22CrossRefGoogle Scholar
  14. 14.
    Gorbea CM. Marchand P. Jiang W, Copeland NG, Gilbert DJ, Jenkins NA, and Bond IS (1993) Cloning, expression, and chromosomal localization of the mouse meprin 0 subunit. J Biol Chem 268: 21035–21043Google Scholar
  15. 15.
    Chestukhin A, Muradov K, Litovchick L, and Shaltiel S (1996) The cleavage of protein kinase A by the kinase-splitting membranal proteinase is reproduced by meprin 0. J Biol Chem 271: 30272–30280PubMedCrossRefGoogle Scholar
  16. 16.
    Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E, and Seiki M (1994) A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature 370: 61–65PubMedCrossRefGoogle Scholar
  17. 17.
    Chantry A, Gregson NA, and Glynn P (1989) A novel metalloproteinase associated with brain myelin membranes. J Biol Chem 264: 21603–21607PubMedGoogle Scholar
  18. 18.
    Hooper NM (1994) Families of zinc metalloproteases. FEBS Lett 354: 1–6PubMedCrossRefGoogle Scholar
  19. 19.
    Jiang W, and Bond JS (1992) Families of metalloendopeptidases and their relationships. FEBS Lett 312: 110–114PubMedCrossRefGoogle Scholar
  20. 20.
    Bennett TA, Lynam EB, Sklar LA, and Roge S (1996) Hydroxamate-based metalloprotease inhibitor blocks shedding of L-selectin adhesion molecule from leukocytes: Functional consequences for neutrophil aggregation. J Immun 156: 3093–3097Google Scholar
  21. 21.
    Kessler E, Takahara K, Biniaminov L, Brusel M, and Greenspan DS (1996) Bone morphogenetic protein-1: The type I procollagen C-proteinase. Science 271: 360–362PubMedCrossRefGoogle Scholar
  22. 22.
    Strongin AY, Collier I, Bannikov G, Marmer BL, Grant GA, and Goldberg GI (1995) Mechanism of cell surface activation of 72-kDa type IV collagenase. J Biol Chem 270: 5331–5338PubMedCrossRefGoogle Scholar
  23. 23.
    Bond JS, and Beynon RJ (1995) The astacin family of metalloendopeptidases. Protein Sci 4: 1247–1261PubMedCrossRefGoogle Scholar
  24. 24.
    Choudry Y, and Kenny AJ (1991) Hydrolysis of transforming growth factor-a by cell-surface peptidases in vitro. Biochem J 280: 57–60PubMedGoogle Scholar
  25. 25.
    Stephenson SL, and Kenny AJ (1988) The metabolism of neuropeptides: Hydrolysis of peptides by the phosphoramidon-insensitive rat kidney enzyme `endopeptidase-2’ and by rat microvillar membranes. Biochem J 255: 45–51PubMedGoogle Scholar
  26. 26.
    Kaushal GP, Walker PD, and Shah SV (1994) An old enzyme with a new function: Purification and characterization of a distinct matrix-degrading metalloproteinase in rat kidney cortex and its identification as meprin. J Cell Bio. 126: 1319–1327Google Scholar
  27. 27.
    Bond JS, and Beynon RJ (1986) Meprin: A membrane-bound metalloendo-peptidase. Curr Top Cell Regul 28: 263–290PubMedGoogle Scholar
  28. 28.
    Yamaguchi T, Kido H, Fukase M, Fujita T, and Katunuma N (1991) A membrane-bound metallo-cndopeptidase from rat kidney hydrolyzing parathyroid hormone. Eur J Biochem 200: 563–571PubMedCrossRefGoogle Scholar
  29. 29.
    Takino T, Sato H, Shinagawa A, and Seiki M (1995) Identification of the second membrane-type matrix metalloproteinase ( MT-MMP) gene from a human placenta cDNA library. J Biol Chem 270: 23013–23020Google Scholar
  30. 30.
    Fox JW, and Bjarnason JB (1996) The reprolysins: a family of metalloproteinases defined by snake venom and mammalian metalloproteinases. In: Zinc Metalloproteases in Health and Disease, NM Hooper, ed. Taylor and Francis Ltd, London, pp. 47–81Google Scholar
  31. 31.
    Rooke J, Pan D, Xu T, and Rubin GM (1996) KUZ, a conserved metalloprotease-disintegrin protein with two roles in Drosophila neurogenesis. Science 273: 1227–1231PubMedCrossRefGoogle Scholar
  32. 32.
    Howard L. and Glynn P (1995) Membrane-associated metalloproteinase recognized by characteristic cleavage of myelin basic protein: Assay and isolation. Methods Enzymol 248: 388–395PubMedCrossRefGoogle Scholar
  33. 33.
    Yagami-Hiromasa T, Sato T, Kurisaki T, Kamijo K, Nabeshima Y, and Fujisawa-Sehara (1995) A metalloprotease-disintegrin participating in myoblast fusion. Nature 377: 652–656PubMedCrossRefGoogle Scholar
  34. 34.
    Wolfsberg TG, Straight PD, Gerena RL, Huovila APJ, Primakoff P. Myles DG. and White JM (1995) ADAM, a widely distributed and developmentally regulated gene family encoding membrane protein with a disintegrin and metalloprotease domain. Dev Biol 169: 378–383Google Scholar
  35. 35.
    Jiang W, Gorbea CM, Flannery AV, Beynon RJ, Grant GA, and Bond, IS (1992) The a subunit of meprin A: Molecular cloning and sequencing, differential expression in inbred mouse strains and evidence for divergent evolution of the a and ß subunits. J Biol Chem 267: 9185–9193Google Scholar
  36. 36.
    Gorbea CM, Flannery AV, and Bond JS (1991) Homo-and heterotetrameric forms of the membrane-hound metalloendopeptidases meprin A and B. Arch Biochem Biophys 290: 549–553PubMedCrossRefGoogle Scholar
  37. 37.
    Marchand P, Tang J, and Bond JS (1994) Membrane association and oligomeric organization of the a and ß subunits of mouse meprin A. J Biol Chem 269: 15388–15393PubMedGoogle Scholar
  38. 38.
    Marchand P, Tang J, Johnson GD, and Bond JS (1995) COOH-terminal proteolytic processing of secreted and membrane foins of the a subunit of the metalloprotease meprin A: Requirement of the I domain for processing in the endoplasmic reticulum. J Biol Chem 270: 5449–5456Google Scholar
  39. 39.
    Beckmann G, and Bork P (1993) An adhesive domain detected in functionally diverse receptors. Trends in Biochem Sci 18: 40–41CrossRefGoogle Scholar
  40. 40.
    Uren AG, and Vaux DL (1996) TRAF proteins and meprins share a conserved domain. Trends in Biochem Sci 21: 244–245Google Scholar
  41. 41.
    Bairoch A (1990) PROSITE: A Dictionary of Protein Sites and Patterns, 6th release, University of Geneva SwitzerlandGoogle Scholar
  42. 42.
    Bond JS, Beynon RJ, Reckelhoff JF, and David CS (1984) Mep-1 gene controlling a kidney metalloendopeptidase is linked to the major histocompatibility complex in mice. Proc Natl Acad Sei USA 81: 5542–5545CrossRefGoogle Scholar
  43. 43.
    Jiang W, Dewald G, Brundage E, Mücher G, Schildhaus H-U, Zerres K, and Bond JS (1995) Fine mapping of MEPI A, the gene encoding the a, subunit of the metalloendopeptidase meprin, to human chromosome 6p21. Biochem Biophys Res Comm 216: 630–635PubMedCrossRefGoogle Scholar
  44. 44.
    Bond JS, Rojas K, Overhauser J, Zoghbi HY, and Jiang W (1995) The structural genes MEPIA and MEPI B, for the a and ß subunits of the metalloendopeptidase meprin map to human chromosome 6p and 18q, respectively. Genomics 25: 300–303PubMedCrossRefGoogle Scholar
  45. 45.
    Craig SS, Reckelhoff JF, and Bond JS (1987) Distribution of meprin in kidneys from mice with high-and low-meprin activity. Am J Physiol 253: C535–0540PubMedGoogle Scholar
  46. 46.
    Beynon RJ, Oliver S, and Robertson DHL (1996) Characterization of the soluble, secreted form of urinary meprin. Biochem J 315: 461–466PubMedGoogle Scholar
  47. 47.
    Boyse EA, Yanakazi K, Yamaguchi M, and Thomas L (1980) Sensory communication amoung mice according to their MHC types. In: The Immune System: Functions and Therapy of Dysfunction, G Doria and A Kshkol, eds, Academic Press, New York, pp 45–53Google Scholar
  48. 48.
    Bankus JM, and Bond JS (1996) Expression and distribution of meprin protease subunits in mouse intestine. Arch Biochem Biophys 331: 87–94PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Judith S. Bond
    • 1
  • Weiping Jiang
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyThe Pennsylvania State University College of MedicineHersheyUSA

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