New Antibiotic Uperin Peptides From the Dorsal Glands of the Australian Toadlet Uperoleia mjobergii

Bradford, AM; Bowie, J.U.; Tyler, MJ; Jc, Wallace

doi:10.1071/ch9961325

Cited by 47 publications

(54 citation statements)

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“…To mimic the zwitterionic nature of peptides at physiological pH (7.4), a charge of +1 and −1 is usually assigned to the first and last backbone atoms of the peptide that is, the N‐ and C‐terminus, respectively. However, in this case, the wild‐type uperin 3.5 is amidated at the C‐terminus, which means that no charge was assigned to the backbone atom at the C‐terminus. Both FA and CG MD were used for simulating the following systems, (a) two uperin 3.5 peptides in a periodic box, and (c) 20 uperin 3.5 peptides in a periodic box, details of which are provided in Table .…”

Section: Methodsmentioning

confidence: 94%

“…An increasing number of anti‐microbial peptides (AMPs) have been identified with an inherent ability to form amyloid structures . Uperin 3.5 (GVGDL 5 IRKAV 10 SVIKN 15 IV‐NH 2 ) is one such broad‐spectrum AMP obtained from the skin secretion of the toadlet Uperoleia mjobergii . Uperin 3.5 is unusual, as it does not aggregate in pure water, but self‐aggregates in saline buffer at neutral pH to form amyloid fibrils .…”

Section: Introductionmentioning

confidence: 99%

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Mechanistic insight into the early stages of amyloid formation using an anuran peptide

et al. 2019

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Uperin 3.5 is a short antimicrobial peptide consisting of 17 Amino acids (GVGDL5IRKAV10SVIKN15IV‐NH2) and is naturally obtained from the skin secretion of Uperoleia mjobergii. It is unusual, as it does not aggregate in pure water, but self‐aggregates to form amyloid fibrils in saline buffer. Hence, it can be used as a model peptide to understand the role of salt in the early stages of amyloid fibril formation. We use molecular dynamics simulations and direct experimental evidence from circular dichroism measurements to investigate the effect of NaCl concentration on interpeptide interactions during the early stages of uperin 3.5 aggregation in water. Our simulations show that addition of salt leads to screening of the positive charges on the R7, K8, and K14 residues by chloride counter‐ions, which in turn results in an increase in the net attraction between the predominantly hydrophobic AVSVI segments of the polypeptide. With addition of salt, changes in interpeptide interactions are accompanied by significant conformational transitions from largely random coil structures in the absence of salt, to greater fractions of α‐helical conformations at higher NaCl concentrations, resulting in greater peptide aggregation at higher NaCl concentrations. Analysis of circular dichroism spectra also shows a similar correlation between an increase in α‐helical content and enhanced aggregation with addition of salt. Thus, the aggregation of uperin 3.5 peptides in presence of salt, results from the combined effects of electrostatic screening, enhanced interaction between hydrophobic residues, and the accompanying conformational changes that stabilize aggregate formation.

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Section: Methodsmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Mechanistic insight into the early stages of amyloid formation using an anuran peptide

et al. 2019

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“…5). A family of structurally related peptides, termed the uperins, has been isolated from the Australian frogs Uperoleia mjoberii [51] and Uperoleia inundata [52] that are active against Gram-positive bacteria. From the species Crinia signifera, two peptides differing by a single amino acid, termed signiferin 2.1 and signiferin 2.2, were identified that are also active against Gram-positive bacteria [53].…”

Section: Myobatrachidaementioning

confidence: 99%

Structural diversity and species distribution of host-defense peptides in frog skin secretions

Conlon

2011

Cell. Mol. Life Sci.

170

147

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Cationic peptides that adopt an amphipathic α-helical conformation in a membrane-mimetic environment are synthesized in the skins of many frog species. These peptides often display cytolytic activities against bacteria and fungi consistent with the idea that they play a role in the host's system of defense against pathogenic microorganisms, but their importance in the survival strategy of the animal is not clearly understood. Despite the common misconception that antimicrobial peptides are synthesized in the skins of all anurans, the species distribution is sporadic, suggesting that their production may confer some evolutionary advantage to the organism but is not necessary for survival. The low potency of many frog skin antimicrobial peptides is consistent with the hypothesis that cutaneous symbiotic bacteria may provide the major system of defense against pathogenic microorganisms in the environment with antimicrobial peptides assuming a supplementary role in some species.

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“…Uperin 3.5 (U3.5, GVGD 5 LIRKA 10 VSVIK 15 NIV‐NH 2 , Figure ) from the toadlet Uperoleia mjobergii is a remarkable AMP that aggregates into amyloid fibrils when dissolved in phosphate buffer at neutral pH . All the uperin peptides tested to date exhibit antimicrobial activity toward a wide range of Gram‐positive bacteria, with U3.5 having the highest propensity for aggregation . As a result, it is an ideal candidate to study both antimicrobial and amyloidogenic mechanisms and the potential association between these two properties.…”

Section: Introductionmentioning

confidence: 99%

Amyloid aggregation and membrane activity of the antimicrobial peptide uperin 3.5

et al. 2018

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Amyloid fibrils are highly ordered, β‐sheet rich forms of aggregated peptides and proteins that are associated with a variety of pathological human disorders, including Alzheimer's and Parkinson's diseases. Amyloid fibril‐forming peptides may be functionally related to antimicrobial peptides, despite differing significantly in sequence and structure. Specifically, their interaction with lipid membranes has mechanistic similarities. The 17‐amino acid peptide uperin 3.5 (U3.5) from an Australian amphibian is antimicrobial and amyloidogenic. Using a quartz crystal microbalance, we investigated the interaction of U3.5 with artificial membranes and found that (i) the membrane interaction of U3.5 is independent of the peptide's aggregation state, (ii) the presence of cholesterol in the membrane dramatically alters peptide–membrane interaction leading to a transmembrane pore‐like arrangement of U3.5, and (iii) electrostatic interaction is important for the membrane activity of U3.5 whereby removal of the positive charge at position 7 of U3.5 enhanced its fibrillar aggregation and ablated its membrane interaction, i.e. there is an inverse relationship between the antimicrobial and amyloidogenic properties of U3.5.

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New Antibiotic Uperin Peptides From the Dorsal Glands of the Australian Toadlet Uperoleia mjobergii

Cited by 47 publications

References 0 publications

Mechanistic insight into the early stages of amyloid formation using an anuran peptide

Mechanistic insight into the early stages of amyloid formation using an anuran peptide

Structural diversity and species distribution of host-defense peptides in frog skin secretions

Amyloid aggregation and membrane activity of the antimicrobial peptide uperin 3.5

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