Arginine in α-defensins: differential effects on bactericidal activity correspond to geometry of membrane curvature generation and peptide-lipid phase behavior.

The Journal of Biological Chemistry
Nathan W SchmidtGerard C L Wong

Abstract

The conserved tridisulfide array of the α-defensin family imposes a common triple-stranded β-sheet topology on peptides that may have highly diverse primary structures, resulting in differential outcomes after targeted mutagenesis. In mouse cryptdin-4 (Crp4) and rhesus myeloid α-defensin-4 (RMAD4), complete substitutions of Arg with Lys affect bactericidal peptide activity very differently. Lys-for-Arg mutagenesis attenuates Crp4, but RMAD4 activity remains mostly unchanged. Here, we show that the differential biological effect of Lys-for-Arg replacements can be understood by the distinct phase behavior of the experimental peptide-lipid system. In Crp4, small-angle x-ray scattering analyses showed that Arg-to-Lys replacements shifted the induced nanoporous phases to a different range of lipid compositions compared with the Arg-rich native peptide, consistent with the attenuation of bactericidal activity by Lys-for-Arg mutations. In contrast, such phases generated by RMAD4 were largely unchanged. The concordance between small-angle x-ray scattering measurements and biological activity provides evidence that specific types of α-defensin-induced membrane curvature-generating tendencies correspond directly to bactericidal activity ...Continue Reading

References

Dec 1, 1989·The Journal of Clinical Investigation·M C TerritoR Lehrer
Aug 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·D M AndersonS Leibler
Dec 1, 1994·Infection and Immunity·S B AleyF D Gillin
Nov 25, 1997·Biophysical Journal·S May, A Ben-Shaul
May 31, 1993·Physical Review Letters·P T SoS Erramilli
Jan 16, 2002·Current Opinion in Immunology·Robert I Lehrer, Tomas Ganz
Jan 25, 2002·Nature·Michael Zasloff
Sep 2, 2003·Nature Reviews. Immunology·Tomas Ganz
Oct 22, 2003·Molecular Immunology·R N Cunliffe
Mar 17, 2004·Peptides·Donald P SatchellAndre J Ouellette
Aug 18, 2004·Nature Materials·Lihua YangGerard C L Wong
Sep 17, 2004·Nature Reviews. Microbiology·Robert I Lehrer
Dec 24, 2004·Antimicrobial Agents and Chemotherapy·Bryan EricksenRobert I Lehrer
May 24, 2005·Nature Immunology·Michael E Selsted, Andre J Ouellette
Nov 23, 2005·Bioinformatics·Konstantin ArnoldTorsten Schwede
Sep 21, 2007·Journal of the American Chemical Society·Lihua YangGerard C L Wong
Oct 4, 2007·Proceedings of the National Academy of Sciences of the United States of America·Lori K SandersGerard C L Wong
Sep 30, 2008·Biochimica Et Biophysica Acta·Richard M Epand, Raquel F Epand
Oct 22, 2008·The Journal of Biological Chemistry·Sheeja VasudevanMelanie J Cocco
Oct 22, 2008·Nucleic Acids Research·Florian KieferTorsten Schwede
Dec 25, 2008·Proceedings of the National Academy of Sciences of the United States of America·Lihua YangGerard C L Wong
Oct 8, 2009·Journal of the American Chemical Society·Abhigyan SomGregory N Tew
Nov 21, 2009·FEBS Letters·Nathan SchmidtGerard C L Wong
Jan 23, 2010·Methods in Molecular Biology·Sharel FigueredoAndré J Ouellette
Apr 9, 2011·Journal of the American Chemical Society·Nathan W SchmidtGerard C L Wong
Jul 19, 2006·Journal of Physics. Condensed Matter : an Institute of Physics Journal·G C ShearmanJ M Seddon
Oct 5, 2011·Proceedings of the National Academy of Sciences of the United States of America·Abhijit MishraGerard C L Wong

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Citations

Apr 30, 2014·Current Opinion in Solid State & Materials Science·Nathan W Schmidt, Gerard C L Wong
Aug 22, 2013·Journal of the American Chemical Society·Nathan W SchmidtGerard C L Wong
May 24, 2014·Biochimica Et Biophysica Acta·Daniel Koller, Karl Lohner
Feb 11, 2015·The Journal of Investigative Dermatology·Nathan W SchmidtGerard C L Wong
Nov 13, 2014·Bioinformatics·Abdullah M KhamisVladimir B Bajic
Mar 19, 2015·PloS One·Himanshu Sharma, Ramakrishnan Nagaraj
Apr 16, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amber KaplanDavid M Underhill
Nov 28, 2013·Current Opinion in Hematology·Le Zhao, Wuyuan Lu
Mar 27, 2015·Journal of Peptide Science : an Official Publication of the European Peptide Society·Himanshu SharmaRamakrishnan Nagaraj
Mar 7, 2017·Frontiers in Neuroscience·Jianguo LiRoger W Beuerman
Apr 11, 2015·Biopolymers·Brittany M deRonde, Gregory N Tew
May 25, 2013·Journal of Computational Chemistry·Birgit HischenhuberBernhard Knapp
Nov 28, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Vladimir N NikolenkoMikhail Y Sinelnikov
May 17, 2019·Current Opinion in Colloid & Interface Science·Michelle W LeeGerard C L Wong
Apr 4, 2020·ACS Infectious Diseases·Acacia F DishmanBrian F Volkman
May 13, 2021·Journal, Genetic Engineering & Biotechnology·S NeelimaRosamma Philip
May 18, 2018·Bioconjugate Chemistry·Michelle W LeeGerard C L Wong
Aug 31, 2013·Biochemistry·Nambirajan RangarajanJames C Weisshaar
Jul 3, 2019·Langmuir : the ACS Journal of Surfaces and Colloids·Cai YaoQi Wang

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