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Christine Ziegler - One of the best experts on this subject based on the ideXlab platform.
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Structural insights into Functional Lipid-protein interactions in secondary transporters.
Biochimica et biophysica acta, 2014Co-Authors: Caroline Koshy, Christine ZieglerAbstract:Abstract Background Structural evidences with Functional corroborations have revealed distinct features of Lipid–protein interactions especially in channels and receptors. Many membrane embedded transporters are also known to require specific Lipids for their functions and for some of them cellular and biochemical data suggest tight regulation by the Lipid bilayer. However, molecular details on Lipid–protein interactions in transporters are sparse since Lipids are either depleted from the detergent solubilized transporters in three-dimensional crystals or not readily resolved in crystal structures. Nevertheless the steady increase in the progress of transporter structure determination contributed more examples of structures with resolved Lipids. Scope of review This review gives an overview on transporter structures in complex with Lipids reported to date and discusses commonly encountered difficulties in the identification of Functionally significant Lipid–protein interactions based on those structures and Functional in vitro data. Recent structures provided molecular details into regulation mechanism of transporters by specific Lipids. The review highlights common findings and conserved patterns for distantly related transporter families to draw a more general picture on the regulatory role of Lipid–protein interactions. Major conclusions Several common themes of the manner in which Lipids directly influence membrane-mediated folding, oligomerization and structure stability can be found. Especially for LeuT-like fold transporters similarities in structurally resolved Lipid–protein interactions suggest a common way in which transporter conformations are affected by Lipids even in evolutionarily distinct transporters. Lipids appear to play an additional role as joints mechanically reinforcing the inverted repeat topology, which is a major determinant in the alternating access mechanism of secondary transporters. General significance This review brings together and adds to the repertoire of knowledge on Lipid–protein interactions of Functional significance presented in structures of membrane transporters. Knowledge of specific Lipid-binding sites and modes of Lipid influence on these proteins not only accomplishes the molecular description of transport cycle further, but also sheds light into localization dependent differences of transporter function. This article is part of a Special Issue entitled Structural biochemistry and biophysics of membrane proteins.
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structural evidence for Functional Lipid interactions in the betaine transporter betp
The EMBO Journal, 2013Co-Authors: Caroline Koshy, Camilo Perez, Christine Ziegler, Eva S Schweikhard, Rebecca M Gartner, Ozkan YildizAbstract:Bilayer Lipids contribute to the stability of membrane transporters and are crucially involved in their proper functioning. However, the molecular knowledge of how surrounding Lipids affect membrane transport is surprisingly limited and despite its general importance is rarely considered in the molecular description of a transport mechanism. One reason is that only few atomic resolution structures of channels or transporters reveal a Functional interaction with Lipids, which are difficult to detect in X-ray structures per se. Overcoming these difficulties, we report here on a new structure of the osmotic stress-regulated betaine transporter BetP in complex with anionic Lipids. This Lipid-associated BetP structure is important in the molecular understanding of osmoregulation due to the strong dependence of activity regulation in BetP on the presence of negatively charged Lipids. We detected eight resolved palmitoyl-oleoyl phosphatidyl glycerol (PG) Lipids mimicking parts of the membrane leaflets and interacting with key residues in transport and regulation. The Lipid–protein interactions observed here in structural detail in BetP provide molecular insights into the role of Lipids in osmoregulated secondary transport.
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structural evidence for Functional Lipid interactions in the betaine transporter betp
Biophysical Journal, 2013Co-Authors: Caroline Koshy, Camilo Perez, Christine Ziegler, Eva S Schweikhard, Rebecca M Gartner, Ozkan YildizAbstract:Bilayer Lipids contribute greatly to the stability of membrane transporters and are crucially involved in their proper functioning. However, the molecular details of how these Lipids affect membrane transport is limited to the few atomic resolution structures of channels and transporters revealing Functional Lipid interactions. As a consequence, despite their biological importance, bilayer Lipid-protein interactions are rarely considered in the molecular description of a transport mechanism, which are difficult to detect in X-ray structures per se. Lipids are often depleted from the detergent-protein complex during isolation or appear too unordered to identify in the crystal. Overcoming these difficulties, we report here on a new structure of the osmotic stress-regulated betaine transporter BetP in complex with anionic Lipids. Activity regulation in BetP depends strongly on the presence of negatively charged Lipids. We observe eight fully resolved palmitoyl-oleoyl phosphatidyl glycerol (PG) Lipids bound to one BetP trimer, mimicking parts of the membrane leaflets. Our data reveal that the PG Lipids interact with key residues in transport and regulation. Lipids, while likely being involved in the correct assembly of the BetP trimer also offer important communication sites between the protomers that might be required during stress sensing and transport regulation. The Lipid-protein interactions observed in BetP reiterate the influence that the surrounding membrane can have on membrane protein function and urge a more holistic approach towards understanding membrane transport, especially for LeuT-like fold transporters.
Kazuo Miyashita - One of the best experts on this subject based on the ideXlab platform.
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The Effect of n-3 PUFA Binding Phosphatidylglycerol on Metabolic Syndrome-Related Parameters and n-3 PUFA Accretion in Diabetic/Obese KK-Ay Mice.
Nutrients, 2019Co-Authors: Liping Chen, Kazuo Miyashita, Naoki Takatani, Fumiaki Beppu, Masashi HosokawaAbstract:n-3 Polyunsaturated fatty acid binding phosphoLipids (n-3 PUFA-PLs) are known to be potent carriers of n-3 PUFAs and provide health benefits. We previously prepared n-3 PUFA binding phosphatidylglycerol (n-3 PUFA-PG) by phospholipase D-mediated transphosphatidylation. Because PG has excellent emulsifiability, n-3 PUFA-PG is expected to work as a Functional molecule with properties of both PG and n-3 PUFAs. In the present study, the health benefits and tissue accretion of dietary n-3 PUFA-PG were examined in diabetic/obese KK-Ay mice. After a feeding duration over 30 days, n-3 PUFA-PG significantly reduced the total and non-HDL cholesterols in the serum of diabetic/obese KK-Ay mice. In the mice fed n-3 PUFA-PG, but not n-3 PUFA-TAG, hepatic Lipid content was markedly alleviated depending on the neutral Lipid reduction compared with the SoyPC-fed mice. Further, the n-3 PUFA-PG diet increased eicosapentaenoic acid and docosahexaenoic acid (DHA) and reduced arachidonic acid in the small intestine, liver, perirenal white adipose tissue, and brain, and the ratio of the n-6 PUFAs to n-3 PUFAs in those tissues became lower compared to the SoyPC-fed mice. Especially, the DHA level was more significantly elevated in the brains of n-3 PUFA-PG-fed mice compared to the SoyPC-fed mice, whereas n-3 PUFA-TAG did not significantly alter DHA in the brain. The present results indicate that n-3 PUFA-PG is a Functional Lipid for reducing serum and liver Lipids and is able to supply n-3 PUFAs to KK-Ay mice.
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spatial and seasonal variations in the bioFunctional Lipid substances fucoxanthin and fucosterol of the laboratory grown edible japanese seaweed sargassum horneri turner cultured in the open sea
Saudi Journal of Biological Sciences, 2017Co-Authors: Masaru Terasaki, Bhaskar Narayan, Chikara Kawagoe, Masashi Hosokawa, Atsushi Ito, Hiroko Kumon, Kazuo MiyashitaAbstract:Abstract This work studied the effect of spatial and seasonal differences on the accumulation of Functional Lipid components in Sargassum horneri (Turner), an edible Japanese seaweed popularly called Akamoku. S. horneri obtained from Samenoura bay area of Japan was laboratory cultured to evaluate the effect of temperature on the accumulation of total Lipids (TL), fucoxanthin (Fx) and fucosterol (Fs) by the alga. The laboratory cultured 3 month old S. horneri were cultured in the open sea in two different geographical locations off Usujiri and Matsushima to evaluate the monthly variations, over a year, in their TL, Fx and Fs contents. S. horneri grown off the Usujiri area accumulated the maximum TL close to 193 mg g−1 dry weight during the coldest part of the year. Fx and Fs contributed 5.6% and 16.2% of the TL in S. horneri harvested off Usujiri in February. Further, in spite of being the same species and parent stock, S. horneri grown off the Matsushima area accumulated less TL, Fx and Fs as compared to their Usujiri counterparts. Our study clearly indicates the role of temperature and light apart from nutritional profile and depth of waters where the seaweed was grown on the accumulation of Functional Lipid components in S. horneri.
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evaluation of recoverable Functional Lipid components of several brown seaweeds phaeophyta from japan with special reference to fucoxanthin and fucosterol contents
Journal of Phycology, 2009Co-Authors: Masaru Terasaki, Atsushi Hirose, Bhaskar Narayan, Yuta Baba, Chikara Kawagoe, Hajime Yasui, Naotsune Saga, Masashi Hosokawa, Kazuo MiyashitaAbstract:Fucoxanthin (Fx) and fucosterol (Fs) are characteristic Lipid components of brown seaweeds that afford several health benefits to humans. This article describes the quantitative evaluation of Lipids of 15 species of brown seaweeds with specific reference to Fx, Fs, and Functional long-chain omega-6/omega-3 polyunsaturated fatty acids (PUFAs). In addition, fatty-acid composition of selected species was also accomplished in the study. Major omega-3 PUFAs in the brown seaweeds analyzed were α-linolenic acid (18:3n-3), octadecatetraenoic acid (18:4n-3), arachidonic acid (20:4n-6), and eicosapentaenoic acid (20:5n-3). Both Fx (mg · g(-1) dry weight [dwt]) and Fs (mg · g(-1) dwt) were determined to be relatively abundant in Sargassum horneri (Turner) C. Agardh (Fx, 3.7 ± 1.6; Fs, 13.4 ± 4.4) and Cystoseira hakodatensis (Yendo) Fensholt (Fx, 2.4 ± 0.9; Fs, 8.9 ± 2.0), as compared with other brown seaweed species. Studies related to seasonal variation in Fx, Fs, and total Lipids of six brown algae [S. horneri, C. hakodatensis, Sargassum fusiforme (Harv.) Setch., Sargassum thunbergii (Mertens ex Roth) Kuntze, Analipus japonicus (Harv.) M. J. Wynne, and Melanosiphon intestinalis (D. A. Saunders) M. J. Wynne] indicated that these Functional Lipid components reached maximum during the period between January and March. The Functional Lipid components present in these seaweeds have the potential for application as nutraceuticals and novel Functional ingredients after their recovery.
Masashi Hosokawa - One of the best experts on this subject based on the ideXlab platform.
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The Effect of n-3 PUFA Binding Phosphatidylglycerol on Metabolic Syndrome-Related Parameters and n-3 PUFA Accretion in Diabetic/Obese KK-Ay Mice.
Nutrients, 2019Co-Authors: Liping Chen, Kazuo Miyashita, Naoki Takatani, Fumiaki Beppu, Masashi HosokawaAbstract:n-3 Polyunsaturated fatty acid binding phosphoLipids (n-3 PUFA-PLs) are known to be potent carriers of n-3 PUFAs and provide health benefits. We previously prepared n-3 PUFA binding phosphatidylglycerol (n-3 PUFA-PG) by phospholipase D-mediated transphosphatidylation. Because PG has excellent emulsifiability, n-3 PUFA-PG is expected to work as a Functional molecule with properties of both PG and n-3 PUFAs. In the present study, the health benefits and tissue accretion of dietary n-3 PUFA-PG were examined in diabetic/obese KK-Ay mice. After a feeding duration over 30 days, n-3 PUFA-PG significantly reduced the total and non-HDL cholesterols in the serum of diabetic/obese KK-Ay mice. In the mice fed n-3 PUFA-PG, but not n-3 PUFA-TAG, hepatic Lipid content was markedly alleviated depending on the neutral Lipid reduction compared with the SoyPC-fed mice. Further, the n-3 PUFA-PG diet increased eicosapentaenoic acid and docosahexaenoic acid (DHA) and reduced arachidonic acid in the small intestine, liver, perirenal white adipose tissue, and brain, and the ratio of the n-6 PUFAs to n-3 PUFAs in those tissues became lower compared to the SoyPC-fed mice. Especially, the DHA level was more significantly elevated in the brains of n-3 PUFA-PG-fed mice compared to the SoyPC-fed mice, whereas n-3 PUFA-TAG did not significantly alter DHA in the brain. The present results indicate that n-3 PUFA-PG is a Functional Lipid for reducing serum and liver Lipids and is able to supply n-3 PUFAs to KK-Ay mice.
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spatial and seasonal variations in the bioFunctional Lipid substances fucoxanthin and fucosterol of the laboratory grown edible japanese seaweed sargassum horneri turner cultured in the open sea
Saudi Journal of Biological Sciences, 2017Co-Authors: Masaru Terasaki, Bhaskar Narayan, Chikara Kawagoe, Masashi Hosokawa, Atsushi Ito, Hiroko Kumon, Kazuo MiyashitaAbstract:Abstract This work studied the effect of spatial and seasonal differences on the accumulation of Functional Lipid components in Sargassum horneri (Turner), an edible Japanese seaweed popularly called Akamoku. S. horneri obtained from Samenoura bay area of Japan was laboratory cultured to evaluate the effect of temperature on the accumulation of total Lipids (TL), fucoxanthin (Fx) and fucosterol (Fs) by the alga. The laboratory cultured 3 month old S. horneri were cultured in the open sea in two different geographical locations off Usujiri and Matsushima to evaluate the monthly variations, over a year, in their TL, Fx and Fs contents. S. horneri grown off the Usujiri area accumulated the maximum TL close to 193 mg g−1 dry weight during the coldest part of the year. Fx and Fs contributed 5.6% and 16.2% of the TL in S. horneri harvested off Usujiri in February. Further, in spite of being the same species and parent stock, S. horneri grown off the Matsushima area accumulated less TL, Fx and Fs as compared to their Usujiri counterparts. Our study clearly indicates the role of temperature and light apart from nutritional profile and depth of waters where the seaweed was grown on the accumulation of Functional Lipid components in S. horneri.
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evaluation of recoverable Functional Lipid components of several brown seaweeds phaeophyta from japan with special reference to fucoxanthin and fucosterol contents
Journal of Phycology, 2009Co-Authors: Masaru Terasaki, Atsushi Hirose, Bhaskar Narayan, Yuta Baba, Chikara Kawagoe, Hajime Yasui, Naotsune Saga, Masashi Hosokawa, Kazuo MiyashitaAbstract:Fucoxanthin (Fx) and fucosterol (Fs) are characteristic Lipid components of brown seaweeds that afford several health benefits to humans. This article describes the quantitative evaluation of Lipids of 15 species of brown seaweeds with specific reference to Fx, Fs, and Functional long-chain omega-6/omega-3 polyunsaturated fatty acids (PUFAs). In addition, fatty-acid composition of selected species was also accomplished in the study. Major omega-3 PUFAs in the brown seaweeds analyzed were α-linolenic acid (18:3n-3), octadecatetraenoic acid (18:4n-3), arachidonic acid (20:4n-6), and eicosapentaenoic acid (20:5n-3). Both Fx (mg · g(-1) dry weight [dwt]) and Fs (mg · g(-1) dwt) were determined to be relatively abundant in Sargassum horneri (Turner) C. Agardh (Fx, 3.7 ± 1.6; Fs, 13.4 ± 4.4) and Cystoseira hakodatensis (Yendo) Fensholt (Fx, 2.4 ± 0.9; Fs, 8.9 ± 2.0), as compared with other brown seaweed species. Studies related to seasonal variation in Fx, Fs, and total Lipids of six brown algae [S. horneri, C. hakodatensis, Sargassum fusiforme (Harv.) Setch., Sargassum thunbergii (Mertens ex Roth) Kuntze, Analipus japonicus (Harv.) M. J. Wynne, and Melanosiphon intestinalis (D. A. Saunders) M. J. Wynne] indicated that these Functional Lipid components reached maximum during the period between January and March. The Functional Lipid components present in these seaweeds have the potential for application as nutraceuticals and novel Functional ingredients after their recovery.
Caroline Koshy - One of the best experts on this subject based on the ideXlab platform.
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Structural insights into Functional Lipid-protein interactions in secondary transporters.
Biochimica et biophysica acta, 2014Co-Authors: Caroline Koshy, Christine ZieglerAbstract:Abstract Background Structural evidences with Functional corroborations have revealed distinct features of Lipid–protein interactions especially in channels and receptors. Many membrane embedded transporters are also known to require specific Lipids for their functions and for some of them cellular and biochemical data suggest tight regulation by the Lipid bilayer. However, molecular details on Lipid–protein interactions in transporters are sparse since Lipids are either depleted from the detergent solubilized transporters in three-dimensional crystals or not readily resolved in crystal structures. Nevertheless the steady increase in the progress of transporter structure determination contributed more examples of structures with resolved Lipids. Scope of review This review gives an overview on transporter structures in complex with Lipids reported to date and discusses commonly encountered difficulties in the identification of Functionally significant Lipid–protein interactions based on those structures and Functional in vitro data. Recent structures provided molecular details into regulation mechanism of transporters by specific Lipids. The review highlights common findings and conserved patterns for distantly related transporter families to draw a more general picture on the regulatory role of Lipid–protein interactions. Major conclusions Several common themes of the manner in which Lipids directly influence membrane-mediated folding, oligomerization and structure stability can be found. Especially for LeuT-like fold transporters similarities in structurally resolved Lipid–protein interactions suggest a common way in which transporter conformations are affected by Lipids even in evolutionarily distinct transporters. Lipids appear to play an additional role as joints mechanically reinforcing the inverted repeat topology, which is a major determinant in the alternating access mechanism of secondary transporters. General significance This review brings together and adds to the repertoire of knowledge on Lipid–protein interactions of Functional significance presented in structures of membrane transporters. Knowledge of specific Lipid-binding sites and modes of Lipid influence on these proteins not only accomplishes the molecular description of transport cycle further, but also sheds light into localization dependent differences of transporter function. This article is part of a Special Issue entitled Structural biochemistry and biophysics of membrane proteins.
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structural evidence for Functional Lipid interactions in the betaine transporter betp
The EMBO Journal, 2013Co-Authors: Caroline Koshy, Camilo Perez, Christine Ziegler, Eva S Schweikhard, Rebecca M Gartner, Ozkan YildizAbstract:Bilayer Lipids contribute to the stability of membrane transporters and are crucially involved in their proper functioning. However, the molecular knowledge of how surrounding Lipids affect membrane transport is surprisingly limited and despite its general importance is rarely considered in the molecular description of a transport mechanism. One reason is that only few atomic resolution structures of channels or transporters reveal a Functional interaction with Lipids, which are difficult to detect in X-ray structures per se. Overcoming these difficulties, we report here on a new structure of the osmotic stress-regulated betaine transporter BetP in complex with anionic Lipids. This Lipid-associated BetP structure is important in the molecular understanding of osmoregulation due to the strong dependence of activity regulation in BetP on the presence of negatively charged Lipids. We detected eight resolved palmitoyl-oleoyl phosphatidyl glycerol (PG) Lipids mimicking parts of the membrane leaflets and interacting with key residues in transport and regulation. The Lipid–protein interactions observed here in structural detail in BetP provide molecular insights into the role of Lipids in osmoregulated secondary transport.
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structural evidence for Functional Lipid interactions in the betaine transporter betp
Biophysical Journal, 2013Co-Authors: Caroline Koshy, Camilo Perez, Christine Ziegler, Eva S Schweikhard, Rebecca M Gartner, Ozkan YildizAbstract:Bilayer Lipids contribute greatly to the stability of membrane transporters and are crucially involved in their proper functioning. However, the molecular details of how these Lipids affect membrane transport is limited to the few atomic resolution structures of channels and transporters revealing Functional Lipid interactions. As a consequence, despite their biological importance, bilayer Lipid-protein interactions are rarely considered in the molecular description of a transport mechanism, which are difficult to detect in X-ray structures per se. Lipids are often depleted from the detergent-protein complex during isolation or appear too unordered to identify in the crystal. Overcoming these difficulties, we report here on a new structure of the osmotic stress-regulated betaine transporter BetP in complex with anionic Lipids. Activity regulation in BetP depends strongly on the presence of negatively charged Lipids. We observe eight fully resolved palmitoyl-oleoyl phosphatidyl glycerol (PG) Lipids bound to one BetP trimer, mimicking parts of the membrane leaflets. Our data reveal that the PG Lipids interact with key residues in transport and regulation. Lipids, while likely being involved in the correct assembly of the BetP trimer also offer important communication sites between the protomers that might be required during stress sensing and transport regulation. The Lipid-protein interactions observed in BetP reiterate the influence that the surrounding membrane can have on membrane protein function and urge a more holistic approach towards understanding membrane transport, especially for LeuT-like fold transporters.
Anne M. Charrier - One of the best experts on this subject based on the ideXlab platform.
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Subpicomolar Iron Sensing Platform Based on Functional Lipid Monolayer Microarrays
Analytical Chemistry, 2016Co-Authors: Ahmad Kenaan, Tuyen D. Nguyen, Herve Dallaporta, Jean-manuel Raimundo, Anne M. CharrierAbstract:We report herein the fabrication of novel micro-arrays based on air-stable Functional Lipid monolayers over silicon using a combination of e-beam lithography and lift-off. We demonstrate these microarrays can be use as ultrasensitive platform for Kelvin probe force microscopy in sensing experiments. Specificity of the detection is given by the Functional group grafted at the Lipid headgroup. The arrays developed for the detection of ferric ions, Fe3+, using a gamma-pyrone derivative chelator, demonstrate subpicomolar limit of detection with high specificity. In addition, the technique takes advantage of the structure of the array with the silicon areas playing the role of reference for the measurement, and we determine critical pattern dimensions below which the probe size/shape impacts the measured results.
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Subpicomolar Iron Sensing Platform Based on Functional Lipid Monolayer Microarrays
2016Co-Authors: Ahmad Kenaan, Tuyen D. Nguyen, Herve Dallaporta, Jean-manuel Raimundo, Anne M. CharrierAbstract:We report herein the fabrication of novel microarrays based on air-stable Functional Lipid monolayers over silicon using a combination of e-beam lithography and lift-off. We demonstrate these microarrays can be use as ultrasensitive platform for Kelvin probe force microscopy in sensing experiments. Specificity of the detection is given by the Functional group grafted at the Lipid headgroup. The arrays developed for the detection of ferric ions, Fe3+, using a γ-pyrone derivative chelator, demonstrate subpicomolar limit of detection with high specificity. In addition, the technique takes advantage of the structure of the array with the silicon areas playing the role of reference for the measurement, and we determine critical pattern dimensions below which the probe size/shape impacts the measured results
