Kinetics of melittin binding to phospholipid small unilamellar vesicles

Sekharam, K. Madhavi; Bradrick, Thomas D.; Georghiou, S.

doi:10.1016/0005-2736(91)90367-h

Cited by 36 publications

(26 citation statements)

References 18 publications

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“…5, A and B) suggested that the substitution of heptadic leucine by alanine had a remarkable effect on the localization of melittin onto the zwitterionic membrane but not onto the negatively charged membrane. The N-terminal of melittin was located slightly inside the zwitterionic membrane, which is consistent with other studies (24,45) whereas the mutants were exposed on its surface. Interestingly, the N termini of both melittin and its analogs were located inside the bilayer of negatively charged lipid vesicles.…”

Section: Discussionsupporting

confidence: 81%

Dissection of Antibacterial and Toxic Activity of Melittin

Asthana¹,

Yadav²,

Ghosh

2004

Journal of Biological Chemistry

198

105

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Melittin, a naturally occurring antimicrobial peptide, exhibits strong lytic activity against both eukaryotic and prokaryotic cells. Despite a tremendous amount of work done, very little is known about the amino acid sequence, which regulates its toxic activity. With the goal of understanding the basis of toxic activity and poor cell selectivity in melittin, a leucine zipper motif has been identified. To evaluate the possible structural and functional roles of this motif, melittin and its two analogs, after substituting the heptadic leucine by alanine, were synthesized and characterized. Functional studies indicated that alanine substitution in the leucine zipper motif resulted in a drastic reduction of the hemolytic activity of melittin. However, interestingly, both the designed analogs exhibited antibacterial activity comparable to melittin. Mutations caused a significant decrease in the membrane permeability of melittin in zwitterionic but not in negatively charged lipid vesicles. Although both the analogs exhibited similar secondary structures in the presence of negatively charged lipid vesicles as melittin, they failed to adopt a significant helical structure in the presence of zwitterionic lipid vesicles. Results suggest that the substitution of heptadic leucine by alanine impaired the assembly of melittin in an aqueous environment and its localization only in zwitterionic but not in negatively charged membrane. Altogether, the results suggest the identification of a structural element in melittin, which probably plays a prominent role in regulating its toxicity but not antibacterial activity. The results indicate that cell selectivity in some antimicrobial peptides can probably be introduced by modulating their assembly in an aqueous environment.

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Section: Discussionsupporting

confidence: 81%

Dissection of Antibacterial and Toxic Activity of Melittin

Asthana¹,

Yadav²,

Ghosh

2004

Journal of Biological Chemistry

198

105

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Section: Melittin As a Model Peptide For Studying Lipid-protein Intermentioning

confidence: 98%

“…The association of melittin with PC membranes takes place in the order of milliseconds (Schwarz and Beschiaschvili 1989;Sekharam et al 1991;Wolfe et al 1998;Constantinescu and Lafleur 2004). The kinetics of the association of melittin with membranes is controversial since both monophasic (Schwarz and Beschiaschvili 1989;Sekharam et al 1991;Constantinescu and Lafleur 2004) as well as biphasic (Constantinescu and Lafleur 2004;Wolfe et al 1998) kinetics have been reported. Melittin adopts an a-helical conformation in membranes which is supported by a number of studies carried out in membrane-mimetic systems such as micelles and reverse micelles, and in liposomes using a variety of techniques (Brown and Wuthrich 1981;Brown et al 1982;Chandani and Balasubramanian 1986;Vogel 1987;Inagaki et al 1989;Ikura et al 1991;Dempsey and Butler 1992;Weaver et al 1992;Bismuto et al 1993;Ghosh et al 1997;Yang et al 2001;Ladokhin and White 2001;Raghuraman and Chattopadhyay 2003;2004a, b, c;.…”

Section: Melittin As a Model Peptide For Studying Lipid-protein Intermentioning

confidence: 98%

“…This has resulted in melittin being used as a convenient and popular model for monitoring lipid-protein interactions in membranes. Melittin is intrinsically fluorescent due to the presence of a single tryptophan residue, Trp-19, which makes it a sensitive probe to study the interaction of melittin with membranes and membrane-mimetic systems (Lauterwein et al 1979;Vogel 1981;Bernard et al 1982;Georghiou et al 1982;Yianni et al 1986;Hermetter and Lakowicz 1986;Chandani and Balasubramanian 1986;Schulze et al 1987;Batenburg et al 1987;John and Jä hnig 1988;Schwarz and Beschiaschvili 1989;Kaszycki and Wasylewski 1990;Sekharam et al 1991;Nishiya and Chou 1991;Weaver et al 1992;Watala and Gwozdzinski 1992;Bismuto et al 1993;Teng and Scarlata 1993;Chattopadhyay and Rukmini 1993;Bradrick et al 1995;van Veen et al 1995;Benachir and Lafleur 1996;Hincha and Crowe 1996;Cajal and Jain 1997;Oren and Shai 1997;Ghosh et al 1997;Wimley and White 2000;Raghuraman and Chattopadhyay 2003;2004a, b, c;Raghuraman et al 2006). This is particularly advantageous since there are no other aromatic amino acids in melittin and this makes interpretation of fluorescence data less complicated due to lack of interference and heterogeneity.…”

Section: Melittin As a Model Peptide For Studying Lipid-protein Intermentioning

confidence: 99%

See 1 more Smart Citation

Melittin: a Membrane-active Peptide with Diverse Functions

2007

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Melittin is the principal toxic component in the venom of the European honey bee Apis mellifera and is a cationic, hemolytic peptide. It is a small linear peptide composed of 26 amino acid residues in which the amino-terminal region is predominantly hydrophobic whereas the carboxy-terminal region is hydrophilic due to the presence of a stretch of positively charged amino acids. This amphiphilic property of melittin has resulted in melittin being used as a suitable model peptide for monitoring lipid-protein interactions in membranes. In this review, the solution and membrane properties of melittin are highlighted, with an emphasis on melittin-membrane interaction using biophysical approaches. The recent applications of melittin in various cellular processes are discussed.

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“…Such interfaces are preferential sites for protein binding to lipid bilayers (Sekharam et al, 1991;Bakás et al, 1996), and equally favored sites for the plentiful ceramide to bind specific sites at the protein. Thus the interdomain interfaces become devices for both the concentration and activation of suitable proteins.…”

Section: Ceramide-induced Protein-protein Contactsmentioning

confidence: 99%