2pco
Spatial Structure and Membrane Permeabilization for Latarcin-1, a Spider Antimicrobial PeptideSpatial Structure and Membrane Permeabilization for Latarcin-1, a Spider Antimicrobial Peptide
Structural highlights
FunctionLAT1_LACTA Has antimicrobial activity against Gram-positive bacteria (A.globiformis VKM Ac-1112 (MIC=0.5 ug/ml), and B.subtilis VKM B-501 (MIC=1.0 ug/ml)), Gram-negative bacteria (E.coli DH5-alpha (MIC=1.0 ug/ml), E.coli MH1 (MIC=0.7 ug/ml), and P.aeruginosa PAO1 (MIC=4.1 ug/ml)), and yeasts (P.pastoris GS115 (MIC=17 ug/ml), and S.cerevisiae Y190 (MIC>33 ug/ml)). Has a moderate hemolytic activity against rabbit erythrocytes. Causes paralysis, but is not lethal when injected into insect (Musca domestica) larvae. Publication Abstract from PubMedLatarcins, linear peptides from the Lachesana tarabaevi spider venom, exhibit a broad-spectrum antimicrobial activity, likely acting on the bacterial cytoplasmic membrane. We study their spatial structures and interaction with model membranes by a combination of experimental and theoretical methods to reveal the structure-activity relationship. In this work, a 26 amino acid peptide, Ltc1, was investigated. Its spatial structure in detergent micelles was determined by (1)H nuclear magnetic resonance (NMR) and refined by Monte Carlo simulations in an implicit water-octanol slab. The Ltc1 molecule was found to form a straight uninterrupted amphiphilic helix comprising 8-23 residues. A dye-leakage fluorescent assay and (31)P NMR spectroscopy established that the peptide does not induce the release of fluorescent marker nor deteriorate the bilayer structure of the membranes. The voltage-clamp technique showed that Ltc1 induces the current fluctuations through planar membranes when the sign of the applied potential coincides with the one across the bacterial inner membrane. This implies that Ltc1 acts on the membranes via a specific mechanism, which is different from the carpet mode demonstrated by another latarcin, Ltc2a, featuring a helix-hinge-helix structure with a hydrophobicity gradient along the peptide chain. In contrast, the hydrophobic surface of the Ltc1 helix is narrow-shaped and extends with no gradient along the axis. We have also disclosed a number of peptides, structurally homologous to Ltc1 and exhibiting similar membrane activity. This indicates that the hydrophobic pattern of the Ltc1 helix and related antimicrobial peptides specifies their activity mechanism. The latter assumes the formation of variable-sized lesions, which depend upon the potential across the membrane. Three-dimensional structure/hydrophobicity of latarcins specifies their mode of membrane activity(,).,Dubovskii PV, Volynsky PE, Polyansky AA, Karpunin DV, Chupin VV, Efremov RG, Arseniev AS Biochemistry. 2008 Mar 18;47(11):3525-33. Epub 2008 Feb 23. PMID:18293934[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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