Large unselective pore in lipid bilayer membrane formed by positively charged peptides containing a sequence of gramicidin A

Antonenko, Yuri N.; Stoilova, Tatyana B.; Kovalchuk, Sergey I.; Egorova, N. S.; Pashkovskaya, Alina A.; Sobko, Alex; Kotova, Еlena А.; Sychev, Sergei V.; Surovoy, Andrey Y.

doi:10.1016/j.febslet.2005.08.049

Cited by 11 publications

(4 citation statements)

References 34 publications

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“…On the other hand, most eukaryotic AMP are broad‐spectrum antimicrobials and many of them are toxic to both bacterial and eukaryotic cells (Asthana et al . 2004; Antonenko et al 2005) whereas most of the bateriocins do not show toxicity to animals at their effective antimicrobial concentration (Kobayashi 2002). Not surprisingly, there is a correlation between their toxicity and specificity: nontoxic and narrow specificity for bacteriocins vs broad‐spectrum and toxicity for eukaryotic AMP.…”

Section: Antimicrobial Peptidesmentioning

confidence: 99%

Novel alternatives to antibiotics: bacteriophages, bacterial cell wall hydrolases, and antimicrobial peptides

et al. 2007

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Summary Extensive research has been conducted on the development of three groups of naturally occurring antimicrobials as novel alternatives to antibiotics: bacteriophages (phages), bacterial cell wall hydrolases (BCWH), and antimicrobial peptides (AMP). Phage therapies are highly efficient, highly specific, and relatively cost‐effective. However, precautions have to be taken in the selection of phage candidates for therapeutic applications as some phages may encode toxins and others may, when integrated into host bacterial genome and converted to prophages in a lysogenic cycle, lead to bacterial immunity and altered virulence. BCWH are divided into three groups: lysozymes, autolysins, and virolysins. Among them, virolysins are the most promising candidates as they are highly specific and have the capability to rapidly lyse antibiotic‐resistant bacteria on a generally species‐specific basis. Finally, AMP are a family of natural proteins produced by eukaryotic and prokaryotic organisms or encoded by phages. AMP are of vast diversity in term of size, structure, mode of action, and specificity and have a high potential for clinical therapeutic applications.

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Section: Antimicrobial Peptidesmentioning

confidence: 99%

Novel alternatives to antibiotics: bacteriophages, bacterial cell wall hydrolases, and antimicrobial peptides

et al. 2007

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“…Therefore, it is unlikely that the roles of Lys and Arg in the membrane-damaging activity of Man-OVA are restricted to phospholipid binding. Several studies revealed that the incorporation of positively charged residues into membrane-damaging peptides could increase their pore-generation activity and the radius of the resulting pore [29,30,31]. Therefore, the functional contribution of Lys and Arg residues to the pore-forming ability of Man-OVA should be considered.…”

Section: Discussionmentioning

confidence: 99%

Ovalbumin with Glycated Carboxyl Groups Shows Membrane-Damaging Activity

Tang

Shi

Chen

et al. 2017

IJMS

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The aim of the present study was to investigate whether glycated ovalbumin (OVA) showed novel activity at the lipid-water interface. Mannosylated OVA (Man-OVA) was prepared by modification of the carboxyl groups with p-aminophenyl α-dextro (d)-mannopyranoside. An increase in the number of modified carboxyl groups increased the membrane-damaging activity of Man-OVA on cell membrane-mimicking vesicles, whereas OVA did not induce membrane permeability in the tested phospholipid vesicles. The glycation of carboxyl groups caused a notable change in the gross conformation of OVA. Moreover, owing to their spatial positions, the Trp residues in Man-OVA were more exposed, unlike those in OVA. Fluorescence quenching studies suggested that the Trp residues in Man-OVA were located on the interface binds with the lipid vesicles, and their microenvironment was abundant in positively charged residues. Although OVA and Man-OVA showed a similar binding affinity for lipid vesicles, the lipid-interacting feature of Man-OVA was distinct from that of OVA. Chemical modification studies revealed that Lys and Arg residues, but not Trp residues, played a crucial role in the membrane-damaging activity of Man-OVA. Taken together, our data suggest that glycation of carboxyl groups causes changes in the structural properties and membrane-interacting features of OVA, generating OVA with membrane-perturbing activities at the lipid-water interface.

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“…28 The gA analogues with C-terminal polycationic extensions also appeared to be able to form unselective pores in lipid membranes. 29,30 The mechanism of formation of pores permeable to fluorescent markers remains unclear, albeit data of fluorescence correlation spectroscopy (FCS) have proved the retention of membrane integrity in the presence of gA analogues. 28 Gramicidin is known to adopt different conformations in diverse solvents and membranes, including head-to-head righthanded single-stranded helical dimers (HD) and parallel and antiparallel (left-and right-handed) double-stranded helical dimers (DH).…”

Section: Introductionmentioning

confidence: 99%

Gramicidin A disassembles large conductive clusters of its lysine-substituted derivatives in lipid membranes

Antonenko

Gluhov

Firsov

et al. 2015

Phys. Chem. Chem. Phys.

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N-terminally substituted lysine derivatives of gramicidin A (gA), [Lys1]gA and [Lys3]gA, but not glutamate- or aspartate-substituted peptides have been previously shown to cause the leakage of carboxyfluorescein from liposomes. Here, the leakage induction was also observed for [Arg1]gA and [Arg3]gA, while [His1]gA and [His3]gA were inactive at neutral pH. The Lys3-containing analogue with all tryptophans replaced by isoleucines did not induce liposome leakage, similar to gA. This suggests that the presence of both tryptophans and N-terminal cationic residues is critical for pore formation. Remarkably, the addition of gA blocked the leakage induced by [Lys3]gA. By examining with fluorescence correlation spectroscopy the peptide-induced leakage of fluorescent markers from liposomes, we estimated the diameter of pores responsible for the leakage to be about 1.6 nm. Transmission electron cryo-microscopy imaging of liposomes with [Lys3]gA showed that the liposomal membranes contained high electron density particles with a size of about 40 Å, suggesting the formation of peptide clusters. No such clusterization was observed in liposomes incorporating gA or a mixture of gA with [Lys3]gA. Three-dimensional reconstruction of the clusters was compatible with their pentameric arrangement. Based on experimental data and computational modeling, we suggest that the large pore formed by [Lys3]gA represents a barrel-stave oligomeric cluster formed by antiparallel double-stranded helical dimers (DH). In a tentative model, the pentamer of dimers may be stabilized by aromatic Trp-Trp and cation-π Trp-Lys interactions between the neighboring DHs. The inhibiting effect of gA on the [Lys3]gA-induced leakage can be attributed to breaking of cation-π interactions, which prevents peptide clusterization and pore formation.

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Large unselective pore in lipid bilayer membrane formed by positively charged peptides containing a sequence of gramicidin A

Cited by 11 publications

References 34 publications

Novel alternatives to antibiotics: bacteriophages, bacterial cell wall hydrolases, and antimicrobial peptides

Novel alternatives to antibiotics: bacteriophages, bacterial cell wall hydrolases, and antimicrobial peptides

Ovalbumin with Glycated Carboxyl Groups Shows Membrane-Damaging Activity

Gramicidin A disassembles large conductive clusters of its lysine-substituted derivatives in lipid membranes

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