Structure of homo- and hetero-oligomeric meprin metalloproteases. Dimers, tetramers, and high molecular mass multimers - PubMed (original) (raw)

. 2003 Jan 24;278(4):2522-32.

doi: 10.1074/jbc.M208808200. Epub 2002 Oct 23.

Affiliations

• PMID: 12399461
• DOI: 10.1074/jbc.M208808200

Free article

Structure of homo- and hetero-oligomeric meprin metalloproteases. Dimers, tetramers, and high molecular mass multimers

Greg P Bertenshaw et al. J Biol Chem. 2003.

Free article

Abstract

Meprin A and B, metalloproteases consisting of evolutionarily related alpha and/or beta subunits, are membrane-bound and secreted enzymes expressed by kidney and intestinal epithelial cells, leukocytes, and cancer cells. Previous work established that the multidomain meprin subunits (each approximately 80 kDa) form disulfide-bridged homo- and heterodimers, and differ in substrate and peptide bond specificities. The work herein clearly demonstrates that meprin dimers differ markedly in their ability to oligomerize. Electrophoresis, light scattering, size exclusion chromatography, and electron microscopy were used to characterize quaternary structures of recombinant rat meprins. Meprin B, consisting of meprin beta subunits only, was dimeric under a wide range of conditions. By contrast, meprin alpha homodimers formed heterogeneous multimers (ring-, circle-, spiral-, and tube-like structures) containing up to 100 subunits, with molecular masses at protein peaks ranging from approximately 1.0 to 6.0 MDa. The size of the meprin alpha homo-oligomers was dependent on protein concentration, ionic strength, and activation state. Meprin alphabeta heterodimers tended to form tetramers but not higher oligomers. Thus, the presence of meprin beta, which has a transmembrane domain in vivo, restricts the oligomerization potential of meprin molecules and localizes meprins to the plasma membrane. By contrast, the propensity of secreted meprin alpha homodimers to self-associate concentrates proteolytic potential into high molecular mass multimers and thus allows for autocompartmentalization. The work indicates that different mechanisms exist to localize and concentrate the proteolytic activity of membrane-bound and secreted meprin metalloproteinases.

PubMed Disclaimer

Similar articles

• Differences in the activation mechanism between the alpha and beta subunits of human meprin.
  Becker C, Kruse MN, Slotty KA, Köhler D, Harris JR, Rösmann S, Sterchi EE, Stöcker W. Becker C, et al. Biol Chem. 2003 May;384(5):825-31. doi: 10.1515/BC.2003.092. Biol Chem. 2003. PMID: 12817480
• Intersubunit and domain interactions of the meprin B metalloproteinase. Disulfide bonds and protein-protein interactions in the MAM and TRAF domains.
  Ishmael FT, Shier VK, Ishmael SS, Bond JS. Ishmael FT, et al. J Biol Chem. 2005 Apr 8;280(14):13895-901. doi: 10.1074/jbc.M414218200. Epub 2005 Feb 4. J Biol Chem. 2005. PMID: 15695509
• Probing the active sites and mechanisms of rat metalloproteases meprin A and B.
  Bertenshaw GP, Villa JP, Hengst JA, Bond JS. Bertenshaw GP, et al. Biol Chem. 2002 Jul-Aug;383(7-8):1175-83. doi: 10.1515/BC.2002.129. Biol Chem. 2002. PMID: 12437103
• Meprin proteolytic complexes at the cell surface and in extracellular spaces.
  Villa JP, Bertenshaw GP, Bylander JE, Bond JS. Villa JP, et al. Biochem Soc Symp. 2003;(70):53-63. doi: 10.1042/bss0700053. Biochem Soc Symp. 2003. PMID: 14587282 Review.
• The metalloproteases meprin α and meprin β: unique enzymes in inflammation, neurodegeneration, cancer and fibrosis.
  Broder C, Becker-Pauly C. Broder C, et al. Biochem J. 2013 Mar 1;450(2):253-64. doi: 10.1042/BJ20121751. Biochem J. 2013. PMID: 23410038 Free PMC article. Review.

Cited by

• Structure and Dynamics of Meprin β in Complex with a Hydroxamate-Based Inhibitor.
  Linnert M, Fritz C, Jäger C, Schlenzig D, Ramsbeck D, Kleinschmidt M, Wermann M, Demuth HU, Parthier C, Schilling S. Linnert M, et al. Int J Mol Sci. 2021 May 26;22(11):5651. doi: 10.3390/ijms22115651. Int J Mol Sci. 2021. PMID: 34073350 Free PMC article.
• Adherens junction proteins in the hamster uterus: their contributions to the success of implantation.
  Luan L, Ding T, Stinnett A, Reese J, Paria BC. Luan L, et al. Biol Reprod. 2011 Nov;85(5):996-1004. doi: 10.1095/biolreprod.110.090126. Epub 2011 Jul 13. Biol Reprod. 2011. PMID: 21753191 Free PMC article.
• Meprin A metalloproteases enhance renal damage and bladder inflammation after LPS challenge.
  Yura RE, Bradley SG, Ramesh G, Reeves WB, Bond JS. Yura RE, et al. Am J Physiol Renal Physiol. 2009 Jan;296(1):F135-44. doi: 10.1152/ajprenal.90524.2008. Epub 2008 Oct 29. Am J Physiol Renal Physiol. 2009. PMID: 18971209 Free PMC article.
• Proteolytic processing and inactivation of CCL2/MCP-1 by meprins.
  Herzog C, Haun RS, Shah SV, Kaushal GP. Herzog C, et al. Biochem Biophys Rep. 2016 Aug 21;8:146-150. doi: 10.1016/j.bbrep.2016.08.019. eCollection 2016 Dec. Biochem Biophys Rep. 2016. PMID: 28955950 Free PMC article.
• Helical ultrastructure of the metalloprotease meprin α in complex with a small molecule inhibitor.
  Bayly-Jones C, Lupton CJ, Fritz C, Venugopal H, Ramsbeck D, Wermann M, Jäger C, de Marco A, Schilling S, Schlenzig D, Whisstock JC. Bayly-Jones C, et al. Nat Commun. 2022 Oct 19;13(1):6178. doi: 10.1038/s41467-022-33893-7. Nat Commun. 2022. PMID: 36261433 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database