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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Peptide:lipid ratio and membrane surface charge determine the mechanism of action of the antimicrobial peptide BP100. Conformational and functional studies

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Manzini, Mariana C. [1] ; Perez, Katia R. [2] ; Riske, Karin A. [2] ; Bozelli, Jr., Jose C. [1] ; Santos, Talita L. [3] ; da Silva, Marcia A. [1] ; Saraiva, Greice K. V. [1] ; Politi, Mario J. [1] ; Valente, Ana P. [3] ; Almeida, Fabio C. L. [3] ; Chaimovich, Hernan [1] ; Rodrigues, Magali A. [4] ; Bemquerer, Marcelo P. [4] ; Schreier, Shirley [1] ; Cuccovia, Iolanda M. [1]
Total Authors: 15
Affiliation:
[1] Univ Sao Paulo, Inst Chem, Dept Biochem, BR-05513970 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Dept Biophys, BR-04044020 Sao Paulo - Brazil
[3] Univ Fed Rio de Janeiro, Inst Med Biochem, Nucl Magnet Resonance Natl Ctr, Rio De Janeiro - Brazil
[4] Embrapa Recursos Genet & Biotecnol, BR-70770917 Brasilia, DF - Brazil
Total Affiliations: 4
Document type: Journal article
Source: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES; v. 1838, n. 7, p. 1985-1999, JUL 2014.
Web of Science Citations: 41
Abstract

The cecropin-melittin hybrid antimicrobial peptide BP100 (H-KKLFKKILKYL-NH2) is selective for Gram-negative bacteria, negatively charged membranes, and weakly hemolytic. We studied BP100 conformational and functional properties upon interaction with large unilamellar vesicles, LUVs, and giant unilamellar vesicles, GUVs, containing variable proportions of phosphatidylcholine (PC) and negatively charged phosphatidylglycerol (PG). CD and NMR spectra showed that upon binding to PG-containing LUVs BP100 acquires a-helical conformation, the helix spanning residues 3-11. Theoretical analyses indicated that the helix is amphipathic and surface-seeking. CD and dynamic light scattering data evinced peptide and/or vesicle aggregation, modulated by peptide: lipid ratio and PG content. BP100 decreased the absolute value of the zeta potential () of LUVs with low PG contents; for higher PG, binding was analyzed as an ion-exchange process. At high salt, BP100-induced LUVS leakage requires higher peptide concentration, indicating that both electrostatic and hydrophobic interactions contribute to peptide binding. While a gradual release took place at low peptide:lipid ratios, instantaneous loss occurred at high ratios, suggesting vesicle disruption. Optical microscopy of GUVs confirmed BP100-promoted disruption of negatively charged membranes. The mechanism of action of BP100 is determined by both peptide:lipid ratio and negatively charged lipid content While gradual release results from membrane perturbation by a small number of peptide molecules giving rise to changes in acyl chain packing, lipid clustering (leading to membrane defects), and/or membrane thinning, membrane disruption results from a sequence of events large-scale peptide and lipid clustering, giving rise to peptide-lipid patches that eventually would leave the membrane in a carpet-like mechanism. (C) 2014 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 07/50970-5 - Chemical and biological reactivity in interfaces
Grantee:Hernan Chaimovich Guralnik
Support type: Research Projects - Thematic Grants
FAPESP's process: 13/08166-5 - Interfacial chemistry: drugs, peptides and ezymes interactions with membrane models
Grantee:Iolanda Midea Cuccovia
Support type: Research Projects - Thematic Grants