Intramolecular inhibition of human defensin HNP-1 by its propiece

The Journal of Clinical Investigation
E V ValoreTomas Ganz

Abstract

We examined mechanisms that protect host defense cells from their cytotoxic effector molecules. Human neutrophil peptides (HNP) 1-3 are microbicidal and cytotoxic defensins, initially synthesized as 94-amino acid preproHNP(1-94), cotranslationally proteolyzed to proHNP(20-94), then converted by removal of the anionic propiece to mature HNP(65-94)(HNP-1 and -3) and HNP(66-94) (HNP-2). We hypothesized that during synthesis and subcellular sorting the anionic propiece inhibits the cytotoxicity of the cationic defensin. We expressed preproHNP-1 cDNA in recombinant baculovirus-infected insect cells that secreted the normally transient proHNP-1(20-94) into the medium. Cyanogen bromide cleaved proHNP-1(20-94) at the fortuitously located Met64 to yield mature recombinant HNP-1(65-94) and unlinked propiece. Recombinant and native HNP-1 purified from PMN were identical as judged by mass spectrometry, retention time in reverse-phase high performance liquid chromatography, migration on acid-urea polyacrylamide gels, and reaction with a conformation-specific antibody. Recombinant and native HNP-1 had comparable microbicidal activity towards Listeria monocytogenes and were similarly potent in permeabilizing K562 leukemia cells, but proHNP-1(...Continue Reading

References

Oct 1, 1992·Immunology Today·J A Hoffmann, C Hetru
Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·B L KaganR I Lehrer
Aug 9, 1991·Journal of Immunological Methods·A V PanyutichT Ganz
Mar 21, 1991·Journal of Immunological Methods·R I LehrerP Eisenhauer
Aug 1, 1989·The Journal of Clinical Investigation·R I LehrerM E Selsted
Oct 1, 1985·The Journal of Clinical Investigation·T GanzR I Lehrer
Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·K A DaherM Kronenberg
Oct 1, 1971·The Journal of Experimental Medicine·D F BaintonM G Farquhar
Sep 1, 1994·Protein Science : a Publication of the Protein Society·W C WimleyS H White
Dec 1, 1993·Current Opinion in Cell Biology·D BakerD A Agard
Jan 1, 1993·Annual Review of Immunology·R I LehrerT Ganz

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Citations

Jun 15, 2007·Inflammatory Bowel Diseases·Jishu Shi
Jun 3, 2005·Springer Seminars in Immunopathology·Andre J Ouellette
Aug 24, 2010·Cell and Tissue Research·Linda Hazlett, Minhao Wu
Feb 23, 2012·Applied Biochemistry and Biotechnology·Nava ChapnikOren Froy
Aug 28, 2004·Comptes rendus biologies·Tomas Ganz
Jul 19, 2005·Journal of Hepatology·Daniel F WallaceV Nathan Subramaniam
Mar 16, 2001·Bioorganic & Medicinal Chemistry·C A ParishJ E Gabay
Jun 20, 2002·Trends in Immunology·Michel Salzet
Aug 26, 1998·Scandinavian Journal of Immunology·H G Boman
May 11, 2012·The Journal of Biological Chemistry·Mohsen RajabiWuyuan Lu
Sep 9, 2008·The Journal of Biological Chemistry·Karishma KamdarAndré J Ouellette
Feb 3, 2009·The Journal of Biological Chemistry·Carole L WilsonWilliam C Parks
Dec 10, 2002·Hybridoma and Hybridomics·Shigeharu KurosawaHiroshige Sasahara
Aug 24, 2002·Biology of Reproduction·Hans Henning von HorstenChristiane Kirchhoff
Feb 28, 2003·Biology of Reproduction·Otto FröhlichLeona G Young
Jan 1, 1996·Inflammatory Bowel Diseases·P R GibsonA J Wilson
Mar 10, 2001·Inflammatory Bowel Diseases·A J Ouellette, C L Bevins
Sep 10, 2009·Antimicrobial Agents and Chemotherapy·Chrystelle DeracheAnne-Christine Lalmanach
Jan 6, 2009·Ophthalmic Research·Alison M McDermott
May 16, 1998·The Journal of Clinical Investigation·E V ValoreT Ganz
Jun 15, 1999·Pediatric Research·K M Huttner, C L Bevins
Feb 26, 2011·World Journal of Gastroenterology : WJG·Mathias Chamaillard, Rodrigue Dessein
May 14, 2014·PloS One·Dong-Qiang ChengJing-Fei Huang
Jun 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·Gregorino PaoneJoel Moss
May 12, 2011·Cellular and Molecular Life Sciences : CMLS·André Joseph Ouellette
Jul 4, 2012·International Journal of Medical Microbiology : IJMM·Ean-jeong SeoTobias A Oelschlaeger
Feb 3, 2009·Journal of Proteomics·Nathalie DroinEric Solary
Apr 26, 2003·The Journal of Investigative Dermatology·Mohamed ZaiouRichard L Gallo
Mar 4, 2008·Veterinary Immunology and Immunopathology·Albert van DijkHenk P Haagsman
Oct 2, 2007·Blood Cells, Molecules & Diseases·Erika V Valore, Tomas Ganz
Mar 16, 2007·Journal of Molecular Biology·Zhibin WuWuyuan Lu
Feb 20, 2009·Journal of Applied Microbiology·L MarquèsP Berthomieu
Feb 22, 2011·Oral Diseases·G Diamond, Lk Ryan
Dec 16, 2011·Immunological Reviews·Robert I Lehrer, Wuyuan Lu
Aug 6, 2004·Protein Expression and Purification·Ingrid CipákováVladimír Velebný
May 5, 2004·Best Practice & Research. Clinical Gastroenterology·Andre J Ouellette

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