Novicidin's membrane permeabilizing activity is driven by membrane partitioning but not by helicity: A biophysical study of the impact of lipid charge and cholesterol

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Novicidin's membrane permeabilizing activity is driven by membrane partitioning but not by helicity : A biophysical study of the impact of lipid charge and cholesterol. / Balakrishnan, Vijay S; Vad, Brian S; Otzen, Daniel.

I: BBA General Subjects, Bind 1834, Nr. 6, 02.04.2013, s. 996-1002.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{b2e6ce9f60de4db1a980f2e87c47a437,
title = "Novicidin's membrane permeabilizing activity is driven by membrane partitioning but not by helicity: A biophysical study of the impact of lipid charge and cholesterol",
abstract = "We have investigated the interactions between the antimicrobial peptide Novicidin (Nc) and vesicles containing the phospholipid DOPC, with various amounts of DOPG and cholesterol using circular dichroism spectroscopy, calcein release, equilibrium dialysis and isothermal titration calorimetry. Nc adopts a random coil structure in the absence of lipids and in the presence of vesicles containing 100% DOPC. Lipids with 25-40% DOPG induce the highest level of helicity in Nc; higher DOPG levels lead to lower helicity levels and an altered tertiary arrangement of the peptide. However, the ability of Nc to permeabilize vesicles correlates not with helicity but rather with its overall membrane affinity, which is enthalpically favorable but opposed by entropy. Permeabilization declines with increasing mole percentage PG. Changes in helicity correlate with changes in enthalpy, reflecting the enthalpy of helix formation, but not with affinity. There is also a large favorable enthalpic interaction between Nc and lipids in the absence of negative charge and structural changes. Cholesterol slightly reduces membrane permeabilization but has little effect on Nc affinity and secondary structure, and probably protects the membrane by inducing the liquid ordered state. We conclude that helicity is not a prerequisite for activity, and charge-charge interactions are not the only major driving force for AMP interactions with membranes. Our data are compatible with a model in which a superficial binding mode with a large membrane surface binding area per peptide is more efficient than a more intimate embedding within the membrane environment.",
author = "Balakrishnan, {Vijay S} and Vad, {Brian S} and Daniel Otzen",
note = "Copyright {\textcopyright} 2013 Elsevier B.V. All rights reserved.",
year = "2013",
month = apr,
day = "2",
doi = "10.1016/j.bbapap.2013.03.025",
language = "English",
volume = "1834",
pages = "996--1002",
journal = "B B A - General Subjects",
issn = "0304-4165",
publisher = "Elsevier BV",
number = "6",

}

RIS

TY - JOUR

T1 - Novicidin's membrane permeabilizing activity is driven by membrane partitioning but not by helicity

T2 - A biophysical study of the impact of lipid charge and cholesterol

AU - Balakrishnan, Vijay S

AU - Vad, Brian S

AU - Otzen, Daniel

N1 - Copyright © 2013 Elsevier B.V. All rights reserved.

PY - 2013/4/2

Y1 - 2013/4/2

N2 - We have investigated the interactions between the antimicrobial peptide Novicidin (Nc) and vesicles containing the phospholipid DOPC, with various amounts of DOPG and cholesterol using circular dichroism spectroscopy, calcein release, equilibrium dialysis and isothermal titration calorimetry. Nc adopts a random coil structure in the absence of lipids and in the presence of vesicles containing 100% DOPC. Lipids with 25-40% DOPG induce the highest level of helicity in Nc; higher DOPG levels lead to lower helicity levels and an altered tertiary arrangement of the peptide. However, the ability of Nc to permeabilize vesicles correlates not with helicity but rather with its overall membrane affinity, which is enthalpically favorable but opposed by entropy. Permeabilization declines with increasing mole percentage PG. Changes in helicity correlate with changes in enthalpy, reflecting the enthalpy of helix formation, but not with affinity. There is also a large favorable enthalpic interaction between Nc and lipids in the absence of negative charge and structural changes. Cholesterol slightly reduces membrane permeabilization but has little effect on Nc affinity and secondary structure, and probably protects the membrane by inducing the liquid ordered state. We conclude that helicity is not a prerequisite for activity, and charge-charge interactions are not the only major driving force for AMP interactions with membranes. Our data are compatible with a model in which a superficial binding mode with a large membrane surface binding area per peptide is more efficient than a more intimate embedding within the membrane environment.

AB - We have investigated the interactions between the antimicrobial peptide Novicidin (Nc) and vesicles containing the phospholipid DOPC, with various amounts of DOPG and cholesterol using circular dichroism spectroscopy, calcein release, equilibrium dialysis and isothermal titration calorimetry. Nc adopts a random coil structure in the absence of lipids and in the presence of vesicles containing 100% DOPC. Lipids with 25-40% DOPG induce the highest level of helicity in Nc; higher DOPG levels lead to lower helicity levels and an altered tertiary arrangement of the peptide. However, the ability of Nc to permeabilize vesicles correlates not with helicity but rather with its overall membrane affinity, which is enthalpically favorable but opposed by entropy. Permeabilization declines with increasing mole percentage PG. Changes in helicity correlate with changes in enthalpy, reflecting the enthalpy of helix formation, but not with affinity. There is also a large favorable enthalpic interaction between Nc and lipids in the absence of negative charge and structural changes. Cholesterol slightly reduces membrane permeabilization but has little effect on Nc affinity and secondary structure, and probably protects the membrane by inducing the liquid ordered state. We conclude that helicity is not a prerequisite for activity, and charge-charge interactions are not the only major driving force for AMP interactions with membranes. Our data are compatible with a model in which a superficial binding mode with a large membrane surface binding area per peptide is more efficient than a more intimate embedding within the membrane environment.

U2 - 10.1016/j.bbapap.2013.03.025

DO - 10.1016/j.bbapap.2013.03.025

M3 - Journal article

C2 - 23562965

VL - 1834

SP - 996

EP - 1002

JO - B B A - General Subjects

JF - B B A - General Subjects

SN - 0304-4165

IS - 6

ER -