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1. Stabilization of supramolecular membrane protein–lipid bilayer assemblies through immobilization in a crystalline exoskeleton

   https://doi.org/10.1038/s41467-021-22285-y  

   Herbert, Fabian C.; Abeyrathna, Sameera S.; Abeyrathna, Nisansala S.; Wijesundara, Yalini H.; Brohlin, Olivia R.; Carraro, Francesco; Amenitsch, Heinz; Falcaro, Paolo; Luzuriaga, Michael A.; Durand-Silva, Alejandra; et al (December 2021, Nature Communications)

   null (Ed.)

   Abstract Artificial native-like lipid bilayer systems constructed from phospholipids assembling into unilamellar liposomes allow the reconstitution of detergent-solubilized transmembrane proteins into supramolecular lipid-protein assemblies called proteoliposomes, which mimic cellular membranes. Stabilization of these complexes remains challenging because of their chemical composition, the hydrophobicity and structural instability of membrane proteins, and the lability of interactions between protein, detergent, and lipids within micelles and lipid bilayers. In this work we demonstrate that metastable lipid, protein-detergent, and protein-lipid supramolecular complexes can be successfully generated and immobilized within zeolitic-imidazole framework (ZIF) to enhance their stability against chemical and physical stressors. Upon immobilization in ZIF bio-composites, blank liposomes, and model transmembrane metal transporters in detergent micelles or embedded in proteoliposomes resist elevated temperatures, exposure to chemical denaturants, aging, and mechanical stresses. Extensive morphological and functional characterization of the assemblies upon exfoliation reveal that all these complexes encapsulated within the framework maintain their native morphology, structure, and activity, which is otherwise lost rapidly without immobilization. 

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2. Lipid-dependent conformational dynamics of bacterial ATP-binding cassette transporter Sav1866

   https://doi.org/10.1101/2024.04.18.590185  

   Badiee, Shadi A; Hettige, Jeevapani; Moradi, Mahmoud (April 2024, bioRxiv)

   Abstract Sav1866, a bacterial ATP-binding cassette (ABC) exporter, plays a crucial role in cellular processes by facilitating the efflux of a diverse range of substrates, including drugs, chemotherapeutic agents, peptides, and lipids. This efflux activity significantly impacts the effectiveness of various therapies against bacterial infections. In our recent investigation, we focused on understanding the conformational dynamics of Sav1866 within different lipid environments. Specifically, we explored its behavior in environments composed of DMPC and POPE lipids, which exhibit crucial distinctions not only in their headgroup polarity but also in the length and saturation of their hydrophobic tails. Our extensive set of equilibrium microsecond-level all-atom molecular dynamics (MD) simulations revealed significant distinctions in transporter behavior influenced by these lipid compositions. We observed a rapid transition to an occluded-inward-facing (IF-occ) conformation in POPE environments, contrasting with a channel-like behavior in DMPC environments, deviating from the expected alternating access mechanism (AAM). These findings underscore the significant impact of lipid compositions on ABC transporter function, offering new perspectives on membrane transport mechanisms. 

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3. Structure and dynamics of lipid membranes interacting with antivirulence end-phosphorylated polyethylene glycol block copolymers

   https://doi.org/10.1039/C9SM01642B  

   Yu, Jing; Mao, Jun; Nagao, Michihiro; Bu, Wei; Lin, Binhua; Hong, Kunlun; Jiang, Zhang; Liu, Yun; Qian, Shuo; Tirrell, Matthew; et al (January 2020, Soft Matter)

   The structure and dynamics of lipid membranes in the presence of extracellular macromolecules are critical for cell membrane functions and many pharmaceutical applications. The pathogen virulence-suppressing end-phosphorylated polyethylene glycol (PEG) triblock copolymer ( Pi-ABAPEG ) markedly changes the interactions with lipid vesicle membranes and prevents PEG-induced vesicle phase separation in contrast to the unphosphorylated copolymer ( ABAPEG ). Pi-ABAPEG weakly absorbs on the surface of lipid vesicle membranes and slightly changes the structure of 1,2-dimyristoyl- sn-glycero -3-phosphocholine ( DMPC ) unilamellar vesicles at 37 °C, as evidenced by small angle neutron scattering. X-ray reflectivity measurements confirm the weak adsorption of Pi-ABAPEG on DMPC monolayer, resulting in a more compact DMPC monolayer structure. Neutron spin-echo results show that the adsorption of Pi-ABAPEG on DMPC vesicle membranes increases the membrane bending modulus κ . 

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4. Spontaneous bilayer wrapping of virus particles by a phospholipid Langmuir monolayer

   Torres-Salgado, J F; Villagrana-Escareño, M V; Duran-Meza, A L; Segovia-Gonzalez, X F; Cadena-Nava, R D; Gelbart, W M; Knobler, C M; RuizGarcia, J (December 2023, European journal of physics)

   We report here the spontaneous formation of lipid-bilayer-wrapped virus particles, following the injection of “naked” virus particles into the subphase of a Langmuir trough with a liquid monolayer of lipids at its air–water interface. The virus particles are those of the well-studied cowpea chlorotic mottle virus, CCMV, which are negatively charged at the pH 6 of the subphase; the lipids are a 9:1 mix of neutral DMPC and cationic CTAB molecules. Before adding CCMV particles to the subphase we establish the mixed lipid monolayer in its liquid-expanded state at a fixed pressure (17.5 mN/m) and average area-per- molecule of (41 ̊A2). Keeping the total area fixed, the surface pressure is observed to decrease at about 15 h after adding the virus particles in the subphase; by 37 h it has dropped to zero, corresponding to essentially all the lipid molecules having been removed from the air–water interface. By collecting particles from the subphase and measuring their sizes by atomic force microscopy, we show that the virus particles have been wrapped by lipid bilayers (or by two lipid bilayers). These results can be understood in terms of thermal fluctuations and electrostatic interactions driving the wrapping of the anionic virus particles by the cationic lipids. 

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5. How do salt and lipids affect conformational dynamics of Aβ42 monomers in water?

   https://doi.org/10.1039/D2CP05044G  

   Andrews, Brian; Ruggiero, Thomas; Urbanc, Brigita (January 2023, Physical Chemistry Chemical Physics)

   It is well established that amyloid β-protein (Aβ) self-assembly is involved in triggering of Alzheimer's disease. On the other hand, evidence of physiological function of Aβ interacting with lipids has only begun to emerge. Details of Aβ–lipid interactions, which may underlie physiological and pathological activities of Aβ, are not well understood. Here, the effects of salt and 1,2-dimyristoyl- sn-glycero -3-phosphocholine (DMPC) lipids on conformational dynamics of Aβ42 monomer in water are examined by all-atom molecular dynamics (MD). We acquired six sets of 250 ns long MD trajectories for each of the three lipid concentrations (0, 27, and 109 mM) in the absence and presence of 150 mM salt. Ten replica trajectories per set are used to enhance sampling of Aβ42 conformational space. We show that salt facilitates long-range tertiary contacts in Aβ42, resulting in more compact Aβ42 conformations. By contrast, addition of lipids results in lipid-concentration dependent Aβ42 unfolding concomitant with enhanced stability of the turn in the A21–A30 region. At the high lipid concentration, salt enables the N-terminal region of Aβ42 to form long-range tertiary contacts and interact with lipids, which results in formation of a parallel β-strand. Aβ42 forms stable lipid–protein complexes whereby the protein is adhered to the lipid cluster rather than embedded into it. We propose that the inability of Aβ42 monomer to get embedded into the lipid cluster may be important for facilitating repair of leaks in the blood-brain barrier without penetrating and damaging cellular membranes. 

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