Cell-lytic and antibacterial peptides that act by perturbing the barrier function of membranes: facets of their conformational features, structure-function correlations and membrane-perturbing abilities

Saberwal, Gayatri; Nagaraj, Ramakrishnan

doi:10.1016/0304-4157(94)90002-7

Cited by 242 publications

(195 citation statements)

References 167 publications

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“…This loop is distinguished by an alternating series of positively charged and hydrophobic residues that, by virtue of the extended fl-conformation, point in opposite directions, and a single pair of positive charges that, because of the fl-turn conformation, point in the same direction and maintain the amphipathicity. Similar structures have been proposed for two other mammalian LPS binding proteins, LBP [16] and BPI [17]. The present CD work is the first to show that indeed CAP18106_[37 adapts a helical conformation when bound to lipid A.…”

Section: Structure Of Cap18jo 6 ~37 In Lipid a Complexsupporting

confidence: 79%

The solution structure of the active domain of CAP18 — a lipopolysaccharide binding protein from rabbit leukocytes

Chen¹,

Brock²,

Luh³

et al. 1995

FEBS Letters

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We have employed the circular dichroism (CD) technique to characterize the solution structure of CAP18~o6_~37, a lipopolysaccharide (LPS) binding, antimicrobial protein, and its interaction with lipid A. Our results revealed that CAP181o6_137 may exist in at least three lipid A concentration-dependent, primarily helix conformations. The 'model' structure of CAP181o6_~37 in 30% (v/v) TFE, determined by nuclear magnetic resonance (NMR) technique, was found to be a complete and very rigid helix. In this conformation, the cationic and hydrophobic groups of CAP18~o6_137 are separated into patches and stripes in such a way that it can favorably interact with lipid A through either coulombic interaction with the diphosphoryl groups or hydrophobic interaction with the fatty acyl chains.

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Section: Structure Of Cap18jo 6 ~37 In Lipid a Complexsupporting

confidence: 79%

The solution structure of the active domain of CAP18 — a lipopolysaccharide binding protein from rabbit leukocytes

Chen¹,

Brock²,

Luh³

et al. 1995

FEBS Letters

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“…It is a small linear peptide composed of 26 amino acids (NH 2 -GIGA-VLKVLTTGLPALISWIKRKRQQ-CONH 2 ) in which the amino-terminal region (residues 1-20) is predominantly hydrophobic whereas the carboxy-terminal region (residues 21-26) is hydrophilic due to the presence of a stretch of positively charged amino acids. This amphiphilic property of melittin makes it water soluble and yet it spontaneously associates with natural and artificial membranes (Dempsey 1990;Sansom 1991;Saberwal and Nagaraj 1994). Such a sequence of amino acids, coupled with its amphiphilic nature, is characteristic of many membrane-bound peptides and putative transmembrane helices of membrane proteins (Dempsey 1990;Shai 1995).…”

Section: Introductionmentioning

confidence: 99%

Effect of micellar charge on the conformation and dynamics of melittin

Raghuraman

Chattopadhyay

2004

Eur Biophys J

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Electrostatic interactions play a crucial role in modulating and stabilizing molecular interactions in membranes and membrane-mimetic systems such as micelles. We have monitored the change in the conformation and dynamics of the cationic hemolytic peptide melittin bound to micelles of various charge types, utilizing fluorescence and circular dichroism (CD) spectroscopy. The sole tryptophan of melittin displays a red-edge excitation shift (REES) of 3-6 nm when bound to anionic, nonionic, and zwitterionic micelles. This suggests that melittin is localized in a restricted environment, probably in the interfacial region of the micelles, and this region offers considerable restriction to the reorientational motion of the solvent dipoles around the excited state tryptophan in melittin. Further, the rotational mobility of melittin is considerably reduced in these micelles and is found to be dependent on the surface charge of micelles. Interestingly, our results show that melittin does not partition into cetyltrimethylammonium bromide (CTAB) micelles owing to electrostatic repulsion between melittin and CTAB micelles, both of which carry a positive charge. In addition, the fluorescence lifetime of melittin is modulated in micelles of different charge types. The lowest mean fluorescence lifetime is observed in the case of melittin bound to anionic sodium dodecyl sulfate (SDS) micelles. CD spectroscopy shows that micelles induce significant helicity to melittin, with maximum helicity being induced in the case of melittin bound to SDS micelles. Fluorescence quenching measurements using the neutral aqueous quencher acrylamide show differential accessibility of melittin in various types of micelles. Taken together, our results show that micellar surface charge can modulate the conformation and dynamics of melittin. These results could be relevant to understanding the role of the surface charge of membranes in the interaction of membrane-active, amphiphilic peptides with membranes.

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“…This concept, which has been useful in the field of peptidic cytotoxins to develop new analogues, and to better understand their mode of action [5][6][7], is still the basis for the rational design of new antimicrobial compounds, i.e. analogues or chimeras of natural products [8], or radically new molecules [9,10].…”

mentioning

confidence: 99%

The antibiotic activity of cationic linear amphipathic peptides: lessons from the action of leucine/lysine copolymers on bacteria of the class Mollicutes

Béven

Castano

Dufourcq

et al. 2003

European Journal of Biochemistry

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Peptides composed of leucyl and lysyl residues (ÔLK peptidesÕ) with different compositions and sequences were compared for their antibacterial activities using cell wall-less bacteria of the class Mollicutes (acholeplasmas, mycoplasmas and spiroplasmas) as targets. The antibacterial activity of the amphipathic a-helical peptides varied with their size, 15 residues being the optimal length, independent of the membrane hydrophobic core thickness and the amount of cholesterol. The 15-residue ideally amphipathic a helix with a +5 positive net charge (KLLKLLLKLLLKLLK) had the strongest antibacterial activity, similar to that of melittin. In contrast, scrambled peptides devoid of amphipathy and the less hydrophobic b-sheeted peptides [(LK) n K], even those 15-residue long, were far less potent than the helical ones. Furthermore, the growth inhibitory activity of the peptides was correlated with their ability to abolish membrane potential. These data are fully consistent with a predominantly flat orientation of LK peptides at the lipid/ water interface and strongly supports that these peptides and probably the linear polycationic amphipathic defence peptides act on bacterial membranes in four main steps according to the ÔcarpetÕ model: (a) interfacial partitioning with accumulation of monomers on the target membrane (limiting step); (b) peptide structural changes (conformation, aggregation, and orientation) induced by interactions with the lipid bilayer (as already shown with liposomes and erythrocytes); (c) plasma membrane permeabilization/ depolarization via a detergent-like effect; and (d) rapid bacterial cell death if the extent of depolarization is maintained above a critical threshold.Keywords: amphipathic peptides; antibacterial activity; bacterial cell death; membrane depolarization; mollicutes.The amphipathic a helix concept helps in understanding the behaviour of very different classes of proteins and peptides, especially those acting on membranes [1][2][3][4]. This concept, which has been useful in the field of peptidic cytotoxins to develop new analogues, and to better understand their mode of action [5][6][7], is still the basis for the rational design of new antimicrobial compounds, i.e. analogues or chimeras of natural products [8], or radically new molecules [9,10].The need to understand their mode of action and improve their efficacy and/or selectivity towards microorganisms led to the synthesis of new active peptides, made possible largely by the progress in solid state synthesis. As a result, a large wealth of information was obtained on many natural peptides endowed with cytotoxic (including antimicrobial) activity. However, answers are still missing regarding: (a) the requirements for optimized activity and selectivity; and (b) the mechanisms of action, especially in bacterial cells. In an effort of rationalization, a minimalistic approach was initiated by the pioneering work of De Grado and Lear [11] using residue substitutions or designing simplified sequences [2,[12][13][14]. Using the very mini...

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Cell-lytic and antibacterial peptides that act by perturbing the barrier function of membranes: facets of their conformational features, structure-function correlations and membrane-perturbing abilities

Cited by 242 publications

References 167 publications

The solution structure of the active domain of CAP18 — a lipopolysaccharide binding protein from rabbit leukocytes

The solution structure of the active domain of CAP18 — a lipopolysaccharide binding protein from rabbit leukocytes

Effect of micellar charge on the conformation and dynamics of melittin

The antibiotic activity of cationic linear amphipathic peptides: lessons from the action of leucine/lysine copolymers on bacteria of the class Mollicutes

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