Special Issue "Protein-Lipid Interactions as Key Regulators of Cell Function"

A special issue of Membranes (ISSN 2077-0375). This special issue belongs to the section "Biological Membrane Functions".

Deadline for manuscript submissions: 15 November 2021.

Special Issue Editor

Prof. Dr. Nikolas Nikolaidis
E-Mail Website
Guest Editor
Department of Biological Science, Center for Applied Biotechnology Studies, and Center for Computational and Applied Mathematics, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92834-6850, USA
Interests: heat-shock response; membrane-associated heat-shock proteins; protein–lipid interactions
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Special Issue Information

Dear Colleagues,

Protein–lipid interactions regulate the subcellular localizations and activities of proteins. Furthermore, many membrane-associated proteins modulate the dynamics of cellular membranes. Therefore, the characterization of the exact mechanisms by which these interactions occur is fundamental to understanding key biological processes. The scope of this Special Issue is to bring together manuscripts that characterize protein–lipid interactions, aiming to understand the organizational principles of cell membranes, elucidate the structure and function of membrane proteins, determine the mechanistic details of these interactions, and develop technologies to study how proteins interact with lipids.

Prof. Dr. Nikolas Nikolaidis
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Membranes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (7 papers)

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Research

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Article
Surface Modification of E. coli Outer Membrane Vesicles with Glycosylphosphatidylinositol-Anchored Proteins: Generating Pro/Eukaryote Chimera Constructs
Membranes 2021, 11(6), 428; https://doi.org/10.3390/membranes11060428 - 04 Jun 2021
Viewed by 1472
Abstract
Extracellular vesicles produced by different types of cells have recently attracted great attention, not only for their role in physiology and pathology, but also because of the emerging applications in gene therapy, vaccine production and diagnostics. Less well known than their eukaryotic counterpart, [...] Read more.
Extracellular vesicles produced by different types of cells have recently attracted great attention, not only for their role in physiology and pathology, but also because of the emerging applications in gene therapy, vaccine production and diagnostics. Less well known than their eukaryotic counterpart, also bacteria produce extracellular vesicles, in the case of the Gram-negative E. coli the main species is termed outer membrane vesicles (OMVs). In this study, we show for the first time the functional surface modification of E. coli OMVs with glycosylphosphatidylinositol (GPI)-anchored protein, exploiting a process variably described as molecular painting or protein engineering in eukaryotic membranes, whereby the lipid part of the GPI anchor inserts in cell membranes. By transferring the process to bacterial vesicles, we can generate a hybrid of perfectly eukaryotic proteins (in terms of folding and post-translational modifications) on a prokaryotic platform. We could demonstrate that two different GPI proteins can be displayed on the same OMV. In addition to fluorescent marker proteins, cytokines, growth factors and antigens canb be potentially transferred, generating a versatile modular platform for a novel vaccine strategy. Full article
(This article belongs to the Special Issue Protein-Lipid Interactions as Key Regulators of Cell Function)
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Article
The C-Terminus of Perilipin 3 Shows Distinct Lipid Binding at Phospholipid-Oil-Aqueous Interfaces
Membranes 2021, 11(4), 265; https://doi.org/10.3390/membranes11040265 - 06 Apr 2021
Cited by 2 | Viewed by 1078
Abstract
Lipid droplets (LDs) are ubiquitously expressed organelles; the only intracellular organelles that contain a lipid monolayer rather than a bilayer. Proteins localize and bind to this monolayer as they do to intracellular lipid bilayers. The mechanism by which cytosolic LD binding proteins recognize, [...] Read more.
Lipid droplets (LDs) are ubiquitously expressed organelles; the only intracellular organelles that contain a lipid monolayer rather than a bilayer. Proteins localize and bind to this monolayer as they do to intracellular lipid bilayers. The mechanism by which cytosolic LD binding proteins recognize, and bind, to this lipid interface remains poorly understood. Amphipathic α-helix bundles form a common motif that is shared between cytosolic LD binding proteins (e.g., perilipins 2, 3, and 5) and apolipoproteins, such as apoE and apoLp-III, found on lipoprotein particles. Here, we use pendant drop tensiometry to expand our previous work on the C-terminal α-helix bundle of perilipin 3 and the full-length protein. We measure the recruitment and insertion of perilipin 3 at mixed lipid monolayers at an aqueous-phospholipid-oil interface. We find that, compared to its C-terminus alone, the full-length perilipin 3 has a higher affinity for both a neat oil/aqueous interface and a phosphatidylcholine (PC) coated oil/aqueous interface. Both the full-length protein and the C-terminus show significantly more insertion into a fully unsaturated PC monolayer, contrary to our previous results at the air-aqueous interface. Additionally, the C-terminus shows a preference for lipid monolayers containing phosphatidylethanolamine (PE), whereas the full-length protein does not. These results strongly support a model whereby both the N-terminal 11-mer repeat region and C-terminal amphipathic α-helix bundle domains of perilipin 3 have distinct lipid binding, and potentially biological roles. Full article
(This article belongs to the Special Issue Protein-Lipid Interactions as Key Regulators of Cell Function)
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Article
Structural Interplays in the Flexible N-Terminus and Scaffolding Domain of Human Membrane Protein Caveolin 3
Membranes 2021, 11(2), 82; https://doi.org/10.3390/membranes11020082 - 22 Jan 2021
Viewed by 517
Abstract
Caveolins are critical for the formation of caveolae, which are small invaginations of the plasma membrane involved in a variety of biological processes. Caveolin 3 (Cav3), one of three caveolin isoforms, is an integral membrane protein mainly expressed in muscle tissues. Although various [...] Read more.
Caveolins are critical for the formation of caveolae, which are small invaginations of the plasma membrane involved in a variety of biological processes. Caveolin 3 (Cav3), one of three caveolin isoforms, is an integral membrane protein mainly expressed in muscle tissues. Although various human diseases associated with Cav3 have been reported, structural characterization of Cav3 in the membrane has not been investigated in enough depth to understand the structure–function relationship. Here, using solution NMR, we characterized membrane association, structural communications, and molecular dynamics of the monomeric Cav3 in detergent micelle environment, particularly focused on the whole N-terminal part that is composed of the flexible N-terminus and the scaffolding domain. The results revealed a complicated structural interplay of the individual segments composing the whole N-terminal part, including the pH-dependent helical region, signature motif-like region, signature motif, and scaffolding domain. Collectively, the present study provides novel structural insights into the whole N-terminal part of Cav3 that plays important biological roles in cellular processes and diseases. In particular, given that several disease-related mutations are located at the whole N-terminal part of Cav3, the sophisticated communications in the whole N-terminal segments are likely to have relevance to the molecular basis of Cav3-related disease. Full article
(This article belongs to the Special Issue Protein-Lipid Interactions as Key Regulators of Cell Function)
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Article
Interaction between the Lentil Lipid Transfer Protein Lc-LTP2 and Its Novel Signal Ligand PI(4,5)P2
Membranes 2020, 10(11), 357; https://doi.org/10.3390/membranes10110357 - 20 Nov 2020
Viewed by 784
Abstract
It is known that plant lipid transfer proteins (LTPs) bind a broad spectrum of ligands including fatty acids (FAs), phospho- and glycolipids, acyl-coenzyme A and secondary metabolites. In this work, we used protein−lipid overlay assays to identify new putative LTP ligands. In our [...] Read more.
It is known that plant lipid transfer proteins (LTPs) bind a broad spectrum of ligands including fatty acids (FAs), phospho- and glycolipids, acyl-coenzyme A and secondary metabolites. In this work, we used protein−lipid overlay assays to identify new putative LTP ligands. In our experiments, the lentil lipid transfer protein Lc-LTP2 as well as LTPs from other plants were shown to bind phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P2). Molecular modeling, 2-p-toluidinonaphthalene-6-sulphonate (TNS) displacement and liposome leakage experiments with Lc-LTP2 and its mutant analogs (R45A, Y80A, R45A/Y80A) were performed to investigate interactions between the protein and PI(4,5)P2. It was shown that PI(4,5)P2 initially interacted with the “bottom” entrance of the protein cavity and after complex formation the large polar head of this ligand was also oriented towards the same entrance. We also found that two highly conserved residues in plant LTPs, Arg45 and Tyr80, played an important role in protein-ligand interactions. Apparently, Arg45 is a key residue for interaction with PI(4,5)P2 during both initial contacting and holding in the protein cavity, while Tyr80 is probably a key amino acid playing an essential role in Lc-LTP2 docking to the membrane. Thus, we assumed that the ability of Lc-LTP2 to bind PI(4,5)P2 suggests the involvement of this protein in plant signal transduction. Full article
(This article belongs to the Special Issue Protein-Lipid Interactions as Key Regulators of Cell Function)
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Article
Simultaneous Quantification of Protein Binding Kinetics in Whole Cells with Surface Plasmon Resonance Imaging and Edge Deformation Tracking
Membranes 2020, 10(9), 247; https://doi.org/10.3390/membranes10090247 - 22 Sep 2020
Cited by 1 | Viewed by 725
Abstract
Most drugs work by binding to receptors on the cell surface. Quantification of binding kinetics between drug and membrane protein is an essential step in drug discovery. Current methods for measuring binding kinetics involve extracting the membrane protein and labeling, and both have [...] Read more.
Most drugs work by binding to receptors on the cell surface. Quantification of binding kinetics between drug and membrane protein is an essential step in drug discovery. Current methods for measuring binding kinetics involve extracting the membrane protein and labeling, and both have issues. Surface plasmon resonance (SPR) imaging has been demonstrated for quantification of protein binding to cells with single-cell resolution, but it only senses the bottom of the cell and the signal diminishes with the molecule size. We have discovered that ligand binding to the cell surface is accompanied by a small cell membrane deformation, which can be used to measure the binding kinetics by tracking the cell edge deformation. Here, we report the first integration of SPR imaging and cell edge tracking methods in a single device, and we use lectin interaction as a model system to demonstrate the capability of the device. The integration enables the simultaneous collection of complementary information provided by both methods. Edge tracking provides the advantage of small molecule binding detection capability, while the SPR signal scales with the ligand mass and can quantify membrane protein density. The kinetic constants from the two methods were cross-validated and found to be in agreement at the single-cell level. The variation of observed rate constant between the two methods is about 0.009 s−1, which is about the same level as the cell-to-cell variations. This result confirms that both methods can be used to measure whole-cell binding kinetics, and the integration improves the reliability and capability of the measurement. Full article
(This article belongs to the Special Issue Protein-Lipid Interactions as Key Regulators of Cell Function)
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Review

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Review
Association of Alpha-Crystallin with Fiber Cell Plasma Membrane of the Eye Lens Accompanied by Light Scattering and Cataract Formation
Membranes 2021, 11(6), 447; https://doi.org/10.3390/membranes11060447 - 15 Jun 2021
Viewed by 1104
Abstract
α-crystallin is a major protein found in the mammalian eye lens that works as a molecular chaperone by preventing the aggregation of proteins and providing tolerance to stress in the eye lens. These functions of α-crystallin are significant for maintaining lens transparency. However, [...] Read more.
α-crystallin is a major protein found in the mammalian eye lens that works as a molecular chaperone by preventing the aggregation of proteins and providing tolerance to stress in the eye lens. These functions of α-crystallin are significant for maintaining lens transparency. However, with age and cataract formation, the concentration of α-crystallin in the eye lens cytoplasm decreases with a corresponding increase in the membrane-bound α-crystallin, accompanied by increased light scattering. The purpose of this review is to summarize previous and recent findings of the role of the: (1) lens membrane components, i.e., the major phospholipids (PLs) and sphingolipids, cholesterol (Chol), cholesterol bilayer domains (CBDs), and the integral membrane proteins aquaporin-0 (AQP0; formally MIP26) and connexins, and (2) α-crystallin mutations and post-translational modifications (PTMs) in the association of α-crystallin to the eye lens’s fiber cell plasma membrane, providing thorough insights into a molecular basis of such an association. Furthermore, this review highlights the current knowledge and need for further studies to understand the fundamental molecular processes involved in the association of α-crystallin to the lens membrane, potentially leading to new avenues for preventing cataract formation and progression. Full article
(This article belongs to the Special Issue Protein-Lipid Interactions as Key Regulators of Cell Function)
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Review
The Role of Lipid Environment in Ganglioside GM1-Induced Amyloid β Aggregation
Membranes 2020, 10(9), 226; https://doi.org/10.3390/membranes10090226 - 09 Sep 2020
Cited by 4 | Viewed by 1252
Abstract
Ganglioside GM1 is the most common brain ganglioside enriched in plasma membrane regions known as lipid rafts or membrane microdomains. GM1 participates in many modulatory and communication functions associated with the development, differentiation, and protection of neuronal tissue. It has, however, been demonstrated [...] Read more.
Ganglioside GM1 is the most common brain ganglioside enriched in plasma membrane regions known as lipid rafts or membrane microdomains. GM1 participates in many modulatory and communication functions associated with the development, differentiation, and protection of neuronal tissue. It has, however, been demonstrated that GM1 plays a negative role in the pathophysiology of Alzheimer’s disease (AD). The two features of AD are the formation of intracellular neurofibrillary bodies and the accumulation of extracellular amyloid β (Aβ). Aβ is a peptide characterized by intrinsic conformational flexibility. Depending on its partners, Aβ can adopt different spatial arrangements. GM1 has been shown to induce specific changes in the spatial organization of Aβ, which lead to enhanced peptide accumulation and deleterious effect especially on neuronal membranes containing clusters of this ganglioside. Changes in GM1 levels and distribution during the development of AD may contribute to the aggravation of the disease. Full article
(This article belongs to the Special Issue Protein-Lipid Interactions as Key Regulators of Cell Function)
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