Characterization of the structure–function relationship of a novel salt-resistant antimicrobial peptide, RR12

Wu, Pingsheng; Lai, Shu-Jung; Fung, Kit-Man; Tseng, Tien‐Sheng

doi:10.1039/d0ra04299d

Cited by 10 publications

(8 citation statements)

References 65 publications

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“…More recently, Wu et al. [35] investigated how the structural properties of RR12 could interact with membranes and the structure attached to membrane‐mimetic micelles. RR12 demonstrated disordered folding for a well‐defined α‐helix structure when interacting with SDS micelles [35].…”

Section: Resultsmentioning

confidence: 99%

“…More recently, Wu et al [35] investigated how the structural properties of RR12 could interact with membranes and the structure attached to membrane-mimetic micelles. RR12 demonstrated disordered folding for a well-defined a-helix structure when interacting with SDS micelles [35]. The structure orientation concentrated from residue Arg2 to Ile7 with the C terminus more exposed to the solvent, and they stated that the helix segment could contribute to bactericidal activity [35].…”

Section: Structural Analysismentioning

confidence: 99%

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Deciphering the structure and mechanism of action of computer‐designed mastoparan peptides

Oshiro,

Freitas,

Rezende

et al. 2023

The FEBS Journal

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Mastoparans are cationic peptides with multifunctional pharmacological properties. Mastoparan‐R1 and mastoparan‐R4 were computationally designed based on native mastoparan‐L from wasps and have improved therapeutic potential for the control of bacterial infections. Here, we evaluated whether these peptides maintain their activity against Escherichia coli strains under a range of salt concentrations. We found that mastoparan‐R1 and mastoparan‐R4 preserved their activity under the conditions tested, including having antibacterial activities at physiological salt concentrations. The overall structure of the peptides was investigated using circular dichroism spectroscopy in a range of solvents. No significant changes in secondary structure were observed (random coil in aqueous solutions and α‐helix in hydrophobic and anionic environments). The three‐dimensional structures of mastoparan‐R1 and mastoparan‐R4 were elucidated through nuclear magnetic resonance spectroscopy, revealing amphipathic α‐helical segments for Leu3‐Ile13 (mastoparan‐R1) and Leu3‐Ile14 (mastoparan‐R4). Possible membrane‐association mechanisms for mastoparan‐R1 and mastoparan‐R4 were investigated through surface plasmon resonance and leakage studies with synthetic POPC and POPC/POPG (4:1) lipid bilayers. Mastoparan‐L had the highest affinity for both membrane systems, whereas the two analogs had weaker association, but improved selectivity for lysing anionic membranes. This finding was also supported by molecular dynamics simulations, in which mastoparan‐R1 and mastoparan‐R4 were found to have greater interactions with bacteria‐like membranes compared with model mammalian membranes. Despite having a few differences in their functional and structural profiles, the mastoparan‐R1 analog stood out with the highest activity, greater bacteriostatic potential, and selectivity for lysing anionic membranes. This study reinforces the potential of mastoparan‐R1 as a drug candidate.

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Section: Resultsmentioning

confidence: 99%

Section: Structural Analysismentioning

confidence: 99%

Deciphering the structure and mechanism of action of computer‐designed mastoparan peptides

Oshiro,

Freitas,

Rezende

et al. 2023

The FEBS Journal

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“…Paramagnetic relaxation enhancement (PRE) arising from the dipolar couplings between protein nuclei and unpaired electrons on spin probes is a versatile NMR technique for characterizing protein structural dynamics and interactions. − In a special PRE experiment designed for membrane proteins (referred to as mPRE), the observed paramagnetic relaxation rates of protein nuclei of interest are induced by spin-labeled lipids doped into the membranes, − which thereby can report on the site-specific interactions between the proteins and membranes. The mPRE has been previously applied to studies of membrane-associated IDPs, ,, which however were restricted to qualitative or empirical analyses. As we noted recently, the mPRE experiment has a unique characteristic that the spin labeling of membrane mimetics (e.g., bicelles and nanodiscs) is nonuniform in nature, which can drastically distort the experimental observables for proteins stably associated with membranes .…”

Section: Introductionmentioning

confidence: 99%

Quantitative Ensemble Interpretation of Membrane Paramagnetic Relaxation Enhancement (mPRE) for Studying Membrane-Associated Intrinsically Disordered Proteins

Jin,

Liu,

et al. 2023

J. Am. Chem. Soc.

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An understanding of the functional role played by a membrane-associated intrinsically disordered protein (IDP) requires characterization of its heterogeneous conformations as well as its poses relative to the membranes, which is of great interest but technically challenging. Here, we explore the membrane paramagnetic relaxation enhancement (mPRE) for constructing ensembles of IDPs that dynamically associate with membrane mimetics incorporating spin-labeled lipids. To accurately interpret the mPRE Γ 2 rates, both the dynamics of IDPs and spin probe molecules are taken into account, with the latter described by a weighted three-dimensional (3D) grid model built based on all-atom simulations. The IDP internal conformations, orientations, and immersion depths in lipid bilayers are comprehensively optimized in the Γ 2 -based ensemble modeling. Our approach is tested and validated on the example of POPG bicelle-bound disordered cytoplasmic domain of CD3ε (CD3ε CD ), a component of the T-cell receptor (TCR) complex. The mPREderived CD3ε CD ensemble provides new insights into the IDP−membrane fuzzy association, in particular for the tyrosine-based signaling motif that plays a critical role in TCR signaling. The comparative analysis of the ensembles for wild-type CD3ε CD and mutants that mimic the mono-and dual-phosphorylation effects suggests a delicate membrane regulatory mechanism for activation and inhibition of the TCR activity.

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“…Attention has been paid to AMP structure-function relationships [3][4][5]. One well-studied example is defensins found in fungi, plants, and animals.…”

Section: Introductionmentioning

confidence: 99%

Structural and Functional Enrichment Analyses for Antimicrobial Peptides

Lo¹,

Xie²,

Chang³

2020

Preprint

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Whether there is any inclination between structures and functions of antimicrobial peptides (AMPs) is a mystery yet to be unraveled. AMPs have various structures associated with many different antimicrobial functions, including antibacterial, anticancer, antifungal, antiparasitic and antiviral activities. However, none has yet reported any antimicrobial functional tendency within a specific category of protein/peptide structures nor any structural tendency of a specific antimicrobial function with respect to AMPs. Here we examine the relationships between structures categorized by three structural classification methods (CATH, SCOP and TM) and seven antimicrobial functions with respect to AMPs using an enrichment analysis. The results show that antifungal activities of AMPs were tightly related to two-layer sandwich structure of CATH, knottin fold of SCOP, and the first structural cluster of TM. The associations with knottin and TM cluster 1 even sustained through the AMPs with a low sequence identity. Besides, another significant mutual enrichment was observed between the third cluster of TM and anti-gram-positive-bacterial/anti-gram-negative-bacterial activities. The findings of the structure-function inclination further our understanding of AMPs and could help us design or discover new therapeutic potential AMPs.

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Characterization of the structure–function relationship of a novel salt-resistant antimicrobial peptide, RR12

Abstract: Antimicrobial peptides (AMPs) are potential candidates in designing new anti-infective agents.

Cited by 10 publications

References 65 publications

Deciphering the structure and mechanism of action of computer‐designed mastoparan peptides

Deciphering the structure and mechanism of action of computer‐designed mastoparan peptides

Quantitative Ensemble Interpretation of Membrane Paramagnetic Relaxation Enhancement (mPRE) for Studying Membrane-Associated Intrinsically Disordered Proteins

Structural and Functional Enrichment Analyses for Antimicrobial Peptides

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