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. 1999 Feb;8(2):439–442. doi: 10.1110/ps.8.2.439

A novel clan of zinc metallopeptidases with possible intramembrane cleavage properties.

A P Lewis 1, P J Thomas 1
PMCID: PMC2144267  PMID: 10048339

Abstract

Computer-based database searching and protein multiple sequence alignment has identified a novel clan of zinc metallopeptidases, which, by phylogenetic analysis, has been shown to contain six subfamilies. The family is characterized by four common transmembrane segments and three conserved sequence motifs. The combination of topology analysis and motif identification has detected three potential Zn2+ coordinating residues. Only two of the sequences of this novel zinc metallopeptidase clan possess any functional annotation, one of which is able to cleave its substrate within a cytosol/transmembrane segment junction. A number of observations suggest that the remaining members of this novel clan may also cleave their substrates within transmembrane segments.

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Selected References

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  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  2. Claros M. G., von Heijne G. TopPred II: an improved software for membrane protein structure predictions. Comput Appl Biosci. 1994 Dec;10(6):685–686. doi: 10.1093/bioinformatics/10.6.685. [DOI] [PubMed] [Google Scholar]
  3. Cserzö M., Wallin E., Simon I., von Heijne G., Elofsson A. Prediction of transmembrane alpha-helices in prokaryotic membrane proteins: the dense alignment surface method. Protein Eng. 1997 Jun;10(6):673–676. doi: 10.1093/protein/10.6.673. [DOI] [PubMed] [Google Scholar]
  4. Cutting S., Roels S., Losick R. Sporulation operon spoIVF and the characterization of mutations that uncouple mother-cell from forespore gene expression in Bacillus subtilis. J Mol Biol. 1991 Oct 20;221(4):1237–1256. doi: 10.1016/0022-2836(91)90931-u. [DOI] [PubMed] [Google Scholar]
  5. Duncan E. A., Davé U. P., Sakai J., Goldstein J. L., Brown M. S. Second-site cleavage in sterol regulatory element-binding protein occurs at transmembrane junction as determined by cysteine panning. J Biol Chem. 1998 Jul 10;273(28):17801–17809. doi: 10.1074/jbc.273.28.17801. [DOI] [PubMed] [Google Scholar]
  6. Hooper N. M. Families of zinc metalloproteases. FEBS Lett. 1994 Oct 31;354(1):1–6. doi: 10.1016/0014-5793(94)01079-x. [DOI] [PubMed] [Google Scholar]
  7. Jonassen I. Efficient discovery of conserved patterns using a pattern graph. Comput Appl Biosci. 1997 Oct;13(5):509–522. doi: 10.1093/bioinformatics/13.5.509. [DOI] [PubMed] [Google Scholar]
  8. Kurisu G., Kinoshita T., Sugimoto A., Nagara A., Kai Y., Kasai N., Harada S. Structure of the zinc endoprotease from Streptomyces caespitosus. J Biochem. 1997 Feb;121(2):304–308. doi: 10.1093/oxfordjournals.jbchem.a021587. [DOI] [PubMed] [Google Scholar]
  9. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  10. Lu S., Cutting S., Kroos L. Sporulation protein SpoIVFB from Bacillus subtilis enhances processing of the sigma factor precursor Pro-sigma K in the absence of other sporulation gene products. J Bacteriol. 1995 Feb;177(4):1082–1085. doi: 10.1128/jb.177.4.1082-1085.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Neuwald A. F., Green P. Detecting patterns in protein sequences. J Mol Biol. 1994 Jun 24;239(5):698–712. doi: 10.1006/jmbi.1994.1407. [DOI] [PubMed] [Google Scholar]
  12. Persson B., Argos P. Topology prediction of membrane proteins. Protein Sci. 1996 Feb;5(2):363–371. doi: 10.1002/pro.5560050221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Rawlings N. D., Barrett A. J. Evolutionary families of metallopeptidases. Methods Enzymol. 1995;248:183–228. doi: 10.1016/0076-6879(95)48015-3. [DOI] [PubMed] [Google Scholar]
  14. Rawson R. B., Zelenski N. G., Nijhawan D., Ye J., Sakai J., Hasan M. T., Chang T. Y., Brown M. S., Goldstein J. L. Complementation cloning of S2P, a gene encoding a putative metalloprotease required for intramembrane cleavage of SREBPs. Mol Cell. 1997 Dec;1(1):47–57. doi: 10.1016/s1097-2765(00)80006-4. [DOI] [PubMed] [Google Scholar]
  15. Sakai J., Duncan E. A., Rawson R. B., Hua X., Brown M. S., Goldstein J. L. Sterol-regulated release of SREBP-2 from cell membranes requires two sequential cleavages, one within a transmembrane segment. Cell. 1996 Jun 28;85(7):1037–1046. doi: 10.1016/s0092-8674(00)81304-5. [DOI] [PubMed] [Google Scholar]
  16. Zvelebil M. J., Barton G. J., Taylor W. R., Sternberg M. J. Prediction of protein secondary structure and active sites using the alignment of homologous sequences. J Mol Biol. 1987 Jun 20;195(4):957–961. doi: 10.1016/0022-2836(87)90501-8. [DOI] [PubMed] [Google Scholar]
  17. von Heijne G. Membrane protein structure prediction. Hydrophobicity analysis and the positive-inside rule. J Mol Biol. 1992 May 20;225(2):487–494. doi: 10.1016/0022-2836(92)90934-c. [DOI] [PubMed] [Google Scholar]

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