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  1. Article: Inimitable Impacts of Ceramides on Lipid Rafts Formed in Artificial and Natural Cell Membranes.

    Kinoshita, Masanao / Matsumori, Nobuaki

    Membranes

    2022  Volume 12, Issue 8

    Abstract: Ceramide is the simplest precursor of sphingolipids and is involved in a variety of biological functions ranging from apoptosis to the immune responses. Although ceramide is a minor constituent of plasma membranes, it drastically increases upon cellular ... ...

    Abstract Ceramide is the simplest precursor of sphingolipids and is involved in a variety of biological functions ranging from apoptosis to the immune responses. Although ceramide is a minor constituent of plasma membranes, it drastically increases upon cellular stimulation. However, the mechanistic link between ceramide generation and signal transduction remains unknown. To address this issue, the effect of ceramide on phospholipid membranes has been examined in numerous studies. One of the most remarkable findings of these studies is that ceramide induces the coalescence of membrane domains termed lipid rafts. Thus, it has been hypothesised that ceramide exerts its biological activity through the structural alteration of lipid rafts. In the present article, we first discuss the characteristic hydrogen bond functionality of ceramides. Then, we showed the impact of ceramide on the structures of artificial and cell membranes, including the coalescence of the pre-existing lipid raft into a large patch called a signal platform. Moreover, we proposed a possible structure of the signal platform, in which sphingomyelin/cholesterol-rich and sphingomyelin/ceramide-rich domains coexist. This structure is considered to be beneficial because membrane proteins and their inhibitors are separately compartmentalised in those domains. Considering the fact that ceramide/cholesterol content regulates the miscibility of those two domains in model membranes, the association and dissociation of membrane proteins and their inhibitors might be controlled by the contents of ceramide and cholesterol in the signal platform.
    Language English
    Publishing date 2022-07-23
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2614641-1
    ISSN 2077-0375
    ISSN 2077-0375
    DOI 10.3390/membranes12080727
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Gold nanoparticle-powered screening of membrane protein-specific lipids from complex lipid mixtures.

    Wangamnuayporn, Supakorn / Kinoshita, Masanao / Kawai, Takayuki / Matsumori, Nobuaki

    Analytical biochemistry

    2023  Volume 687, Page(s) 115447

    Abstract: Membrane proteins (MPs) are affected by binding of specific lipids. We previously developed a methodology for systematically analyzing MP-lipid interactions leveraging surface plasmon resonance (SPR). In this method, the gold sensor chip surface was ... ...

    Abstract Membrane proteins (MPs) are affected by binding of specific lipids. We previously developed a methodology for systematically analyzing MP-lipid interactions leveraging surface plasmon resonance (SPR). In this method, the gold sensor chip surface was modified with a self-assembled monolayer (SAM), which allowed for a larger amount of MP-immobilization. However, the laborious lipid purification step remained a bottleneck. To address this issue, a new strategy has been developed utilizing gold nanoparticles (AuNPs) instead of the gold sensor chip. AuNPs were coated with SAM, on which MP was covalently anchored. The MP-immobilized AuNPs were mixed with a lipid mixture, and the recovered lipids were quantified by LC-MS. Bacteriorhodopsin (bR) was used as an MP to demonstrate this concept. We optimized immobilization conditions and confirmed the efficient immobilization of bR by dynamic light scattering and electron micrographs. Washing conditions for pulldown experiments were optimized to efficiently remove non-specific lipids. A new binding index was introduced to qualitatively reproduce the known affinity of lipids for bR. Consequently, the low-abundant and least-studied lipid S-TeGD was identified as a candidate for bR-specific lipids. This technique can skip the laborious lipid purification process, accelerating the screening of MP-specific lipids from complex lipid mixtures.
    MeSH term(s) Membrane Lipids ; Gold ; Membrane Proteins ; Metal Nanoparticles ; Surface Plasmon Resonance/methods
    Chemical Substances Membrane Lipids ; Gold (7440-57-5) ; Membrane Proteins
    Language English
    Publishing date 2023-12-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1110-1
    ISSN 1096-0309 ; 0003-2697
    ISSN (online) 1096-0309
    ISSN 0003-2697
    DOI 10.1016/j.ab.2023.115447
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  3. Article ; Online: Truncated derivatives of amphidinol 3 reveal the functional role of polyol chain in sterol-recognition and pore formation.

    Matsumori, Nobuaki / Hieda, Manami / Morito, Masayuki / Wakamiya, Yuma / Oishi, Tohru

    Bioorganic & medicinal chemistry letters

    2023  Volume 98, Page(s) 129594

    Abstract: Here we examined the membrane binding and pore formation of amphidinol 3 (AM3) and its truncated synthetic derivatives. Importantly, both of the membrane affinity and pore formation activity were well correlated with the reported antifungal activity. Our ...

    Abstract Here we examined the membrane binding and pore formation of amphidinol 3 (AM3) and its truncated synthetic derivatives. Importantly, both of the membrane affinity and pore formation activity were well correlated with the reported antifungal activity. Our data clearly demonstrated that the C1-C30 moiety of AM3 plays essential roles both in sterol recognition and stable pore formation. Based on the current findings, we updated the interacting model between AM3 and sterol, in which the moiety encompassing from C21 to C67 accommodates a sterol molecule with forming hydrogen bonds with the sterol hydroxy group and van der Waals contact between AM3 polyol and sterol skeleton. Although the conformation of the C1-C20 moiety of AM3 is hard to specify due to its flexibility, the region likely contributes to stabilization of pore structure.
    MeSH term(s) Sterols/pharmacology ; Sterols/chemistry ; Amphidinols ; Alkenes/chemistry ; Pyrans/chemistry
    Chemical Substances Sterols ; polyol ; Immunoferon (87139-86-4) ; amphidinol 3 ; Amphidinols ; Alkenes ; Pyrans
    Language English
    Publishing date 2023-12-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 1063195-1
    ISSN 1464-3405 ; 0960-894X
    ISSN (online) 1464-3405
    ISSN 0960-894X
    DOI 10.1016/j.bmcl.2023.129594
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  4. Article: Molecular substructure of the liquid-ordered phase formed by sphingomyelin and cholesterol: sphingomyelin clusters forming nano-subdomains are a characteristic feature.

    Murata, Michio / Matsumori, Nobuaki / Kinoshita, Masanao / London, Erwin

    Biophysical reviews

    2022  Volume 14, Issue 3, Page(s) 655–678

    Abstract: As a model of lipid rafts, the liquid-ordered (Lo) phase formed by sphingomyelin (SM) and cholesterol (Cho) in bilayer membranes has long attracted the attention of biophysics researchers. New approaches and methodologies have led to a better ... ...

    Abstract As a model of lipid rafts, the liquid-ordered (Lo) phase formed by sphingomyelin (SM) and cholesterol (Cho) in bilayer membranes has long attracted the attention of biophysics researchers. New approaches and methodologies have led to a better understanding of the molecular basis of the Lo domain structure. This review summarizes studies on model membrane systems consisting of SM/unsaturated phospholipid/Cho implying that the Lo phase contains SM-based nanodomains (or nano-subdomains). Some of the Lo phase properties may be attributed to these nanodomains. Several studies suggest that the nanodomains contain clustered SM molecules packed densely to form gel-phase-like subdomains of single-digit nanometer size at physiological temperatures. Cho and unsaturated lipids located in the Lo phase are likely to be concentrated at the boundaries between the subdomains. These subdomains are not readily detected in the Lo phase formed by saturated phosphatidylcholine (PC) molecules, suggesting that they are strongly stabilized by homophilic interactions specific to SM, e.g., between SM amide groups. This model for the Lo phase is supported by experiments using dihydro-SM, which is thought to have stronger homophilic interactions than SM, as well as by studies using the enantiomer of SM having opposite stereochemistry to SM at the 2 and 3 positions and by some molecular dynamics (MD) simulations of lipid bilayers containing Lo-lipids. Nanosized gel subdomains seem to play an important role in controlling membrane organization and function in biological membranes.
    Language English
    Publishing date 2022-06-11
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2486483-3
    ISSN 1867-2469 ; 1867-2450
    ISSN (online) 1867-2469
    ISSN 1867-2450
    DOI 10.1007/s12551-022-00967-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Impact of sphingomyelin acyl chain heterogeneity upon properties of raft-like membranes.

    Hirano, Kana / Kinoshita, Masanao / Matsumori, Nobuaki

    Biochimica et biophysica acta. Biomembranes

    2022  Volume 1864, Issue 12, Page(s) 184036

    Abstract: Sphingomyelin (SM) is a main component of lipid rafts and characteristic of abundance of long and saturated acyl chains. Recently, we reported that fluorescence-labeled lipids including C16:0 and C18:0SMs retained membrane behaviors of inherent lipids. ... ...

    Abstract Sphingomyelin (SM) is a main component of lipid rafts and characteristic of abundance of long and saturated acyl chains. Recently, we reported that fluorescence-labeled lipids including C16:0 and C18:0SMs retained membrane behaviors of inherent lipids. Here, we newly prepared fluorescent SMs with longer acyl chains, C22:0 and C24:1, for observing their partition and diffusion in SM/cholesterol (chol)/dioleoylphosphatidylcholine (DOPC) bilayers. Although fluorescent C24:1SM underwent a uniform distribution between ordered (Lo) and disordered (Ld) phases, other fluorescent SMs with saturated acyl chains were preferentially distributed in the Lo phase. Interestingly, when the acyl chains of fluorescent and membrane SMs are different, distribution of fluorescent SM to the Lo phase was reduced compared to when the acyl chains are the same. This tendency was also observed for C16:0SM/C22:0SM/chol/DOPC quaternary bilayers, where the minor SM was more excluded out of the Lo phase than the major SM. We also found that the coexistence of SMs induces SM efflux out of the Lo phase and simultaneous DOPC influx to the Lo phase, consequently reducing the difference in fluidity between the two phases. These results suggest that physicochemical properties of lipid rafts are regulated by the acyl chain heterogeneity of SMs.
    MeSH term(s) Cholesterol/chemistry ; Membrane Microdomains/chemistry ; Membranes ; Sphingomyelins/chemistry
    Chemical Substances Sphingomyelins ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2022-08-30
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 60-7
    ISSN 1879-2642 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2642 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbamem.2022.184036
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Amphidinol 3 preferentially binds to cholesterol in disordered domains and disrupts membrane phase separation.

    Hieda, Manami / Sorada, Akira / Kinoshita, Masanao / Matsumori, Nobuaki

    Biochemistry and biophysics reports

    2021  Volume 26, Page(s) 100941

    Abstract: Amphidinol 3 (AM3), a polyhydroxy-polyene metabolite from the ... ...

    Abstract Amphidinol 3 (AM3), a polyhydroxy-polyene metabolite from the dinoflagellate
    Language English
    Publishing date 2021-02-10
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2831046-9
    ISSN 2405-5808 ; 2405-5808
    ISSN (online) 2405-5808
    ISSN 2405-5808
    DOI 10.1016/j.bbrep.2021.100941
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  7. Article ; Online: Chemical diversity and mode of action of natural products targeting lipids in the eukaryotic cell membrane.

    Nishimura, Shinichi / Matsumori, Nobuaki

    Natural product reports

    2020  Volume 37, Issue 5, Page(s) 677–702

    Abstract: Covering: up to 2019Nature furnishes bioactive compounds (natural products) with complex chemical structures, yet with simple, sophisticated molecular mechanisms. When natural products exhibit their activities in cells or bodies, they first have to bind ... ...

    Abstract Covering: up to 2019Nature furnishes bioactive compounds (natural products) with complex chemical structures, yet with simple, sophisticated molecular mechanisms. When natural products exhibit their activities in cells or bodies, they first have to bind or react with a target molecule in/on the cell. The cell membrane is a major target for bioactive compounds. Recently, our understanding of the molecular mechanism of interactions between natural products and membrane lipids progressed with the aid of newly-developed analytical methods. New technology reconnects old compounds with membrane lipids, while new membrane-targeting molecules are being discovered through the screening for antimicrobial potential of natural products. This review article focuses on natural products that bind to eukaryotic membrane lipids, and includes clinically important molecules and key research tools. The chemical diversity of membrane-targeting natural products and the molecular basis of lipid recognition are described. The history of how their mechanism was unveiled, and how these natural products are used in research are also mentioned.
    MeSH term(s) Animals ; Biological Products/chemistry ; Biological Products/pharmacology ; Cell Membrane/chemistry ; Cell Membrane/drug effects ; Cell Membrane/metabolism ; Eukaryotic Cells/drug effects ; Humans ; Membrane Lipids/chemistry ; Membrane Lipids/metabolism
    Chemical Substances Biological Products ; Membrane Lipids
    Language English
    Publishing date 2020-02-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2002546-4
    ISSN 1460-4752 ; 0265-0568
    ISSN (online) 1460-4752
    ISSN 0265-0568
    DOI 10.1039/c9np00059c
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  8. Article ; Online: Cardiolipin binding enhances KcsA channel gating via both its specific and dianion-monoanion interchangeable sites.

    Iwamoto, Masayuki / Morito, Masayuki / Oiki, Shigetoshi / Nishitani, Yudai / Yamamoto, Daisuke / Matsumori, Nobuaki

    iScience

    2023  Volume 26, Issue 12, Page(s) 108471

    Abstract: KcsA is a potassium channel with a plethora of structural and functional information, but its activity in the KcsA-producing actinomycete membranes remains elusive. To determine lipid species involved in channel-modulation, a surface plasmon resonance ( ... ...

    Abstract KcsA is a potassium channel with a plethora of structural and functional information, but its activity in the KcsA-producing actinomycete membranes remains elusive. To determine lipid species involved in channel-modulation, a surface plasmon resonance (SPR)-based methodology, characterized by immobilization of membrane proteins under a membrane environment, was applied. Dianionic cardiolipin (CL) showed extremely higher affinity for KcsA than monoanionic lipids. The SPR experiments further demonstrated that CL bound not only to the N-terminal M0 helix, a lipid-sensor domain, but to the M0 helix-deleted mutant. In contrast, monoanionic lipids interacted primarily with the M0 helix. This indicates the presence of an alternative CL-binding site, plausibly in the transmembrane domain. Single-channel recordings demonstrated that CL enhanced channel opening in an M0-independent manner. Taken together, the action of monoanionic lipids is exclusively mediated by the M0 helix, while CL binds both the M0 helix and its specific site, further enhancing the channel activity.
    Language English
    Publishing date 2023-11-14
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2023.108471
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Recent advances in microscale separation techniques for lipidome analysis.

    Kawai, Takayuki / Matsumori, Nobuaki / Otsuka, Koji

    The Analyst

    2021  Volume 146, Issue 24, Page(s) 7418–7430

    Abstract: This review paper highlights the recent research on liquid-phase microscale separation techniques for lipidome analysis over the last 10 years, mainly focusing on capillary liquid chromatography (LC) and capillary electrophoresis (CE) coupled with mass ... ...

    Abstract This review paper highlights the recent research on liquid-phase microscale separation techniques for lipidome analysis over the last 10 years, mainly focusing on capillary liquid chromatography (LC) and capillary electrophoresis (CE) coupled with mass spectrometry (MS). Lipids are one of the most important classes of biomolecules which are involved in the cell membrane, energy storage, signal transduction, and so on. Since lipids include a variety of hydrophobic compounds including numerous structural isomers, lipidomes are a challenging target in bioanalytical chemistry. MS is the key technology that comprehensively identifies lipids; however, separation techniques like LC and CE are necessary prior to MS detection in order to avoid ionization suppression and resolve structural isomers. Separation techniques using μm-scale columns, such as a fused silica capillary and microfluidic device, are effective at realizing high-resolution separation. Microscale separation usually employs a nL-scale flow, which is also compatible with nanoelectrospray ionization-MS that achieves high sensitivity. Owing to such analytical advantages, microscale separation techniques like capillary/microchip LC and CE have been employed for more than 100 lipidome studies. Such techniques are still being evolved and achieving further higher resolution and wider coverage of lipidomes. Therefore, microscale separation techniques are promising as the fundamental technology in next-generation lipidome analysis.
    MeSH term(s) Chromatography, Liquid ; Electrophoresis, Capillary ; Lipidomics ; Lipids ; Mass Spectrometry
    Chemical Substances Lipids
    Language English
    Publishing date 2021-12-06
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 210747-8
    ISSN 1364-5528 ; 0003-2654
    ISSN (online) 1364-5528
    ISSN 0003-2654
    DOI 10.1039/d1an00967b
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  10. Article ; Online: Cardiolipin binding enhances KcsA channel gating via both its specific and dianion-monoanion interchangeable sites

    Masayuki Iwamoto / Masayuki Morito / Shigetoshi Oiki / Yudai Nishitani / Daisuke Yamamoto / Nobuaki Matsumori

    iScience, Vol 26, Iss 12, Pp 108471- (2023)

    2023  

    Abstract: Summary: KcsA is a potassium channel with a plethora of structural and functional information, but its activity in the KcsA-producing actinomycete membranes remains elusive. To determine lipid species involved in channel-modulation, a surface plasmon ... ...

    Abstract Summary: KcsA is a potassium channel with a plethora of structural and functional information, but its activity in the KcsA-producing actinomycete membranes remains elusive. To determine lipid species involved in channel-modulation, a surface plasmon resonance (SPR)-based methodology, characterized by immobilization of membrane proteins under a membrane environment, was applied. Dianionic cardiolipin (CL) showed extremely higher affinity for KcsA than monoanionic lipids. The SPR experiments further demonstrated that CL bound not only to the N-terminal M0 helix, a lipid-sensor domain, but to the M0 helix-deleted mutant. In contrast, monoanionic lipids interacted primarily with the M0 helix. This indicates the presence of an alternative CL-binding site, plausibly in the transmembrane domain. Single-channel recordings demonstrated that CL enhanced channel opening in an M0-independent manner. Taken together, the action of monoanionic lipids is exclusively mediated by the M0 helix, while CL binds both the M0 helix and its specific site, further enhancing the channel activity.
    Keywords Biological sciences ; Biochemistry ; Membrane architecture ; Science ; Q
    Subject code 572 ; 500
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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