Structural and functional characterization of the membrane-permeabilizing activity of Nicotiana occidentalis defensin NoD173 and protein engineering to enhance oncolysis

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Fung T LayMark D Hulett

Abstract

Defensins are an extensive family of host defense peptides found ubiquitously across plant and animal species. In addition to protecting against infection by pathogenic microorganisms, some defensins are selectively cytotoxic toward tumor cells. As such, defensins have attracted interest as potential antimicrobial and anticancer therapeutics. The mechanism of defensin action against microbes and tumor cells appears to be conserved and involves the targeting and disruption of cellular membranes. This has been best defined for plant defensins, which upon binding specific phospholipids, such as phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid, form defensin-lipid oligomeric complexes that destabilize membranes, leading to cell lysis. In this study, to further define the anticancer and therapeutic properties of plant defensins, we have characterized a novel plant defensin, Nicotiana occidentalis defensin 173 (NoD173), from N. occidentalis. NoD173 at low micromolar concentrations selectively killed a panel of tumor cell lines over normal primary cells. To improve the anticancer activity of NoD173, we explored increasing cationicity by mutation, with NoD173 with the substitution of Q22 with lysine [NoD173(Q22K)], in...Continue Reading

References

Jun 11, 1986·Nucleic Acids Research·G von Heijne
May 1, 1995·The Plant Cell·F R TerrasJ Vanderleyden
Sep 16, 2000·Trends in Microbiology·R E Hancock, G Diamond
Mar 20, 2003·Plant Physiology·Fung T LayMarilyn A Anderson
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jan 11, 2005·Current Protein & Peptide Science·F T Lay, M A Anderson
Feb 11, 2005·Nature Reviews. Microbiology·Kim A Brogden
Jun 24, 2006·The Plant Journal : for Cell and Molecular Biology·Marie MirouzeLaurence Marquès
Jul 25, 2006·Expert Opinion on Investigational Drugs·Jamie S Mader, David W Hoskin
Dec 13, 2006·Nature Biotechnology·Robert E W Hancock, Hans-Georg Sahl
Dec 15, 2007·Biochimica Et Biophysica Acta·David W Hoskin, Ayyalusamy Ramamoorthy
Mar 15, 2008·The Journal of Biological Chemistry·Nicole L van der WeerdenMarilyn A Anderson
Nov 21, 2008·Acta Crystallographica. Section D, Biological Crystallography·Tobias BeckGeorge M Sheldrick
Oct 20, 2009·European Journal of Pharmacology·Frank Schweizer
Nov 3, 2009·Drug Discovery Today·Patrick VliegheMichel Khrestchatisky
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Dec 17, 2011·Nature Reviews. Drug Discovery·Christopher D FjellGisbert Schneider
Mar 24, 2012·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Fung T LayMarc Kvansakul
Apr 19, 2012·The Journal of Biological Chemistry·Fung T LayMark D Hulett
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Sep 11, 2013·Molecular Plant Pathology·Peter M DracatosMarilyn A Anderson
Sep 17, 2013·ELife·Andrew MorinPiotr Sliz
Mar 8, 2016·Nature Communications·Peter A MeyerPiotr Sliz
Jun 15, 2016·Molecular Biology and Evolution·Thomas M A ShafeeMarilyn A Anderson
Aug 26, 2016·Cellular and Molecular Life Sciences : CMLS·Thomas M A ShafeeMark D Hulett
Sep 21, 2016·Proceedings of the National Academy of Sciences of the United States of America·Marc KvansakulMark D Hulett
Jan 14, 2017·Frontiers in Cellular and Infection Microbiology·Margit MahlapuuCamilla Björn
Jan 24, 2018·Immunology and Cell Biology·Thanh Kha PhanMark D Hulett
Feb 13, 2018·Seminars in Cell & Developmental Biology·Kathy ParisiMarilyn A Anderson

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Citations

Jul 30, 2020·International Journal of Molecular Sciences·Valentina KovalevaIrina V Nesmelova
Dec 6, 2019·Scientific Reports·Santhasiri OrrapinSorasak Intorasoot
Jun 25, 2021·Journal of Chemical Information and Modeling·Pietro G A AronicaChandra S Verma

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