scholarly journals Membrane Interactions of Latarcins: Antimicrobial Peptides from Spider Venom

2021 ◽  
Vol 22 (18) ◽  
pp. 10156
Author(s):  
Parvesh Wadhwani ◽  
Saiguru Sekaran ◽  
Erik Strandberg ◽  
Jochen Bürck ◽  
Archana Chugh ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Coiled Coil ◽  
Bound State ◽  
Spider Venom ◽  
15N Nmr ◽  
Lipid Interactions ◽  
Group Of Seven ◽  
Artificial Lipid Bilayers ◽  
Membrane Bound ◽  
Intracellular Targets

A group of seven peptides from spider venom with diverse sequences constitute the latarcin family. They have been described as membrane-active antibiotics, but their lipid interactions have not yet been addressed. Using circular dichroism and solid-state 15N-NMR, we systematically characterized and compared the conformation and helix alignment of all seven peptides in their membrane-bound state. These structural results could be correlated with activity assays (antimicrobial, hemolysis, fluorescence vesicle leakage). Functional synergy was not observed amongst any of the latarcins. In the presence of lipids, all peptides fold into amphiphilic α-helices as expected, the helices being either surface-bound or tilted in the bilayer. The most tilted peptide, Ltc2a, possesses a novel kind of amphiphilic profile with a coiled-coil-like hydrophobic strip and is the most aggressive of all. It indiscriminately permeabilizes natural membranes (antimicrobial, hemolysis) as well as artificial lipid bilayers through the segregation of anionic lipids and possibly enhanced motional averaging. Ltc1, Ltc3a, Ltc4a, and Ltc5a are efficient and selective in killing bacteria but without causing significant bilayer disturbance. They act rather slowly or may even translocate towards intracellular targets, suggesting more subtle lipid interactions. Ltc6a and Ltc7, finally, do not show much antimicrobial action but can nonetheless perturb model bilayers.

scholarly journals In Silico Study of the Mechanism of Binding of the N-Terminal Region of α Synuclein to Synaptic-Like Membranes

Life ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 98 ◽  
Author(s):  
Carlos Navarro-Paya ◽  
Maximo Sanz-Hernandez ◽  
Alfonso De Simone
Keyword(s):  
Lipid Bilayers ◽  
Conformational Transition ◽  
Md Simulations ◽  
Bound State ◽  
Terminal Region ◽  
Coarse Grained ◽  
Biological Behavior ◽  
In Silico Study ◽  
Membrane Bound ◽  
Presynaptic Protein

The membrane binding by α-synuclein (αS), a presynaptic protein whose aggregation is strongly linked with Parkinson’s disease, influences its biological behavior under functional and pathological conditions. This interaction requires a conformational transition from a disordered-unbound to a partially helical membrane-bound state of the protein. In the present study, we used enhanced coarse-grained MD simulations to characterize the sequence and conformational determinants of the binding to synaptic-like vesicles by the N-terminal region of αS. This region is the membrane anchor and is of crucial importance for the properties of the physiological monomeric state of αS as well as for its aberrant aggregates. These results identify the key factors that play a role in the binding of αS with synaptic lipid bilayers in both membrane-tethered and membrane-locked conformational states.

scholarly journals A Comparative Study on Interactions of Antimicrobial Peptides L- and D-phenylseptin with 1,2-dimyristoyl-sn-glycero-3-phosphocholine

2019 ◽  
Vol 9 (13) ◽  
pp. 2601 ◽  
Author(s):  
Batsaikhan Mijiddorj ◽  
Yuta Matsuo ◽  
Hisako Sato ◽  
Kazuyoshi Ueda ◽  
Izuru Kawamura
Keyword(s):  
Circular Dichroism ◽  
Antimicrobial Peptides ◽  
Lipid Bilayers ◽  
Binding Constants ◽  
Bound State ◽  
Dynamics Simulation ◽  
Membrane Bound ◽  
The Difference ◽  
Α Helix ◽  
Circular Dichroïsm

L-phenylseptin (L-Phes) and D-phenylseptin (D-Phes) are amphibian antimicrobial peptides isolated from the skin secretion of Hypsiboas punctatus. In the N-termini, L-Phes and D-Phes contain three consecutive phenylalanine residues, l-Phe-l-Phe-l-Phe and l-Phe-d-Phe-l-Phe, respectively. They are known to exhibit antimicrobial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Xanthomonas axonopodis pv. Glycines. However, their mechanism of action and the role of the D-amino acid residue have not been elucidated yet. In this study, the interactions of both peptides with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) were investigated by means of quartz crystal microbalance, circular dichroism, vibrational circular dichroism, 31P solid-state NMR, and molecular dynamics simulation. Both peptides have similar binding constants to the DMPC lipid bilayers, in the order of 106 M−1, and form an α-helix structure in the DMPC lipid bilayers. Both the peptides induce similar changes in the dynamics of DMPC lipids. Thus, in spite of the difference in the conformations caused by the chirality at the N-terminus, the peptides showed similar behavior in the membrane-bound state, experimentally and computationally.

scholarly journals Formation of artificial lipid bilayers using droplet dielectrophoresis

Lab on a Chip ◽  
2008 ◽  
Vol 8 (10) ◽  
pp. 1617 ◽  
Author(s):  
Sara Aghdaei ◽  
Mairi E. Sandison ◽  
Michele Zagnoni ◽  
Nicolas G. Green ◽  
Hywel Morgan
Keyword(s):  
Lipid Bilayers ◽  
Artificial Lipid Bilayers

scholarly journals A synergy between mechanosensitive calcium- and membrane-binding mediates tension-sensing by C2-like domains

2021 ◽  
Vol 119 (1) ◽  
pp. e2112390119
Author(s):  
Zhouyang Shen ◽  
Kalina T. Belcheva ◽  
Mark Jelcic ◽  
King Lam Hui ◽  
Anushka Katikaneni ◽  
...  
Keyword(s):  
Lipid Bilayers ◽  
Membrane Insertion ◽  
C2 Domain ◽  
Hydrophobic Membrane ◽  
Membrane Recruitment ◽  
Calcium Dependent ◽  
Nuclear Membranes ◽  
Cytosolic Phospholipase ◽  
Artificial Lipid Bilayers ◽  
Quantitative Basis

When nuclear membranes are stretched, the peripheral membrane enzyme cytosolic phospholipase A2 (cPLA2) binds via its calcium-dependent C2 domain (cPLA2-C2) and initiates bioactive lipid signaling and tissue inflammation. More than 150 C2-like domains are encoded in vertebrate genomes. How many of them are mechanosensors and quantitative relationships between tension and membrane recruitment remain unexplored, leaving a knowledge gap in the mechanotransduction field. In this study, we imaged the mechanosensitive adsorption of cPLA2 and its C2 domain to nuclear membranes and artificial lipid bilayers, comparing it to related C2-like motifs. Stretch increased the Ca2+ sensitivity of all tested domains, promoting half-maximal binding of cPLA2 at cytoplasmic resting-Ca2+ concentrations. cPLA2-C2 bound up to 50 times tighter to stretched than to unstretched membranes. Our data suggest that a synergy of mechanosensitive Ca2+ interactions and deep, hydrophobic membrane insertion enables cPLA2-C2 to detect stretched membranes with antibody-like affinity, providing a quantitative basis for understanding mechanotransduction by C2-like domains.

scholarly journals Nanogold as a Specific Marker for Electron Cryotomography

2009 ◽  
Vol 15 (3) ◽  
pp. 183-188 ◽  
Author(s):  
Yongning He ◽  
Grant J. Jensen ◽  
Pamela J. Bjorkman
Keyword(s):  
Lipid Bilayers ◽  
Outer Surface ◽  
Three Dimensional ◽  
Fc Receptor ◽  
Specific Marker ◽  
Neonatal Fc Receptor ◽  
Membrane Bound ◽  
Nanogold Particles ◽  
Intracellular Vesicles ◽  
Electron Cryotomography

AbstractWhile electron cryotomography (ECT) provides “molecular” resolution, three-dimensional images of unique biological specimens, sample crowdedness, and/or resolution limitations can make it difficult to identify specific macromolecular components. Here we used a 1.4 nm Nanogold® cluster specifically attached to the Fc fragment of IgG to monitor its interaction with the neonatal Fc receptor (FcRn), a membrane-bound receptor that transports IgG across cells in acidic intracellular vesicles. ECT was used to image complexes formed by Nanogold-labeled Fc bound to FcRn attached to the outer surface of synthetic liposomes. In the resulting three-dimensional reconstructions, 1.4 nm Nanogold particles were distributed predominantly along the interfaces where 2:1 FcRn-Fc complexes bridged adjacent lipid bilayers. These results demonstrate that the 1.4 nm Nanogold cluster is visible in tomograms of typically thick samples (∼250 nm) recorded with defocuses appropriate for large macromolecules and is thus an effective marker.

scholarly journals The Dynamics of the Neuropeptide Y Receptor Type 1 Investigated by Solid-State NMR and Molecular Dynamics Simulation

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5489
Author(s):  
Alexander Vogel ◽  
Mathias Bosse ◽  
Marcel Gauglitz ◽  
Sarah Wistuba ◽  
Peter Schmidt ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Solid State ◽  
Neuropeptide Y ◽  
Solid State Nmr ◽  
Bound State ◽  
Receptor Activation ◽  
Order Parameters ◽  
Dynamics Simulation ◽  
15N Nmr

We report data on the structural dynamics of the neuropeptide Y (NPY) G-protein-coupled receptor (GPCR) type 1 (Y1R), a typical representative of class A peptide ligand GPCRs, using a combination of solid-state NMR and molecular dynamics (MD) simulation. First, the equilibrium dynamics of Y1R were studied using 15N-NMR and quantitative determination of 1H-13C order parameters through the measurement of dipolar couplings in separated-local-field NMR experiments. Order parameters reporting the amplitudes of the molecular motions of the C-H bond vectors of Y1R in DMPC membranes are 0.57 for the Cα sites and lower in the side chains (0.37 for the CH2 and 0.18 for the CH3 groups). Different NMR excitation schemes identify relatively rigid and also dynamic segments of the molecule. In monounsaturated membranes composed of longer lipid chains, Y1R is more rigid, attributed to a higher hydrophobic thickness of the lipid membrane. The presence of an antagonist or NPY has little influence on the amplitude of motions, whereas the addition of agonist and arrestin led to a pronounced rigidization. To investigate Y1R dynamics with site resolution, we conducted extensive all-atom MD simulations of the apo and antagonist-bound state. In each state, three replicas with a length of 20 μs (with one exception, where the trajectory length was 10 μs) were conducted. In these simulations, order parameters of each residue were determined and showed high values in the transmembrane helices, whereas the loops and termini exhibit much lower order. The extracellular helix segments undergo larger amplitude motions than their intracellular counterparts, whereas the opposite is observed for the loops, Helix 8, and termini. Only minor differences in order were observed between the apo and antagonist-bound state, whereas the time scale of the motions is shorter for the apo state. Although these relatively fast motions occurring with correlation times of ns up to a few µs have no direct relevance for receptor activation, it is believed that they represent the prerequisite for larger conformational transitions in proteins.

Functional reconstitution of receptors in artificial lipid bilayers

1987 ◽  
Vol 81 (1-2) ◽  
pp. 133-138 ◽  
Author(s):  
Vitaly Vodyanoy ◽  
Dominique Muller ◽  
Kathryn Kramer ◽  
Gary Lynch ◽  
Michel Baudry
Keyword(s):  
Lipid Bilayers ◽  
Artificial Lipid Bilayers
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