Cholesterol-Induced Conformational Change in the Sphingomyelin Headgroup

Shinya Hanashima, Kazuhiro Murakami, Michihiro Yura, Yo Yano, Yuichi Umegawa, Hiroshi Tsuchikawa, Nobuaki Matsumori, Sangjae Seo, Wataru Shinoda, Michio Murata

研究成果: ジャーナルへの寄稿記事

抄録

Sphingomyelin (SM) and cholesterol (Cho) are the important lipids for the formation of biologically functional membrane domains, lipid rafts. However, the interaction between Cho and the headgroup of SM remains unclear. In this study, we performed solid-state NMR experiments to reveal the Cho effects on the headgroup conformation using 2H-labeled stearoyl-SM (SSM). Deuterated SSMs at the Cα, Cβ, and Cγ positions of a choline moiety were separately prepared and subjected to NMR measurements to determine the quadrupolar splitting of 2H signals in hydrated SSM unitary and SSM/Cho (1:1) bilayers. Using 2H NMR and 13C-31P REDOR data, the conformation and orientation of the choline moiety were deduced and compared with those derived from molecular dynamics simulations. In SSM unitary bilayers, three torsional angles in the phosphocholine moiety, P-O-Cα-Cβ, were found to be consecutive +gauche(g)/+g/+g or −g/−g/−g. The orientation and conformation of the SSM headgroup were consistent with the results of our molecular dynamics simulations and the previous results on phosphatidylcholines. The quadrupolar coupling at the α methylene group slightly increased in the presence of Cho, and those at the Cβ and Cγ decreased more significantly, thus suggesting that Cho reduced the gauche conformation at the Cα-Cβ torsion. The conformational ensemble in the presence of Cho may enhance the so-called umbrella effect of the SSM headgroup, resulting in the stabilization of Cho near the SM molecules by concealing the hydrophobic Cho core from interfacial water. We also examined the effect of the chiral centers at the sphingosine chain to the headgroup conformation by determining the enantiomeric excess between the diastereomeric +g/+g/+g and −g/−g/−g conformers using (S)-Cα-deuterated and (R)-Cα-deuterated SSMs. Their 2H NMR measurements showed that the chiral centers induced the slight diastereomeric excess in the SM headgroup conformation.

元の言語英語
ページ(範囲)307-318
ページ数12
ジャーナルBiophysical Journal
117
発行部数2
DOI
出版物ステータス出版済み - 7 23 2019

Fingerprint

Sphingomyelins
Cholesterol
Molecular Dynamics Simulation
Choline
Sphingosine
Phosphorylcholine
Membrane Lipids
Phosphatidylcholines
Lipids
Water

All Science Journal Classification (ASJC) codes

  • Biophysics

これを引用

Hanashima, S., Murakami, K., Yura, M., Yano, Y., Umegawa, Y., Tsuchikawa, H., ... Murata, M. (2019). Cholesterol-Induced Conformational Change in the Sphingomyelin Headgroup. Biophysical Journal, 117(2), 307-318. https://doi.org/10.1016/j.bpj.2019.06.019

Cholesterol-Induced Conformational Change in the Sphingomyelin Headgroup. / Hanashima, Shinya; Murakami, Kazuhiro; Yura, Michihiro; Yano, Yo; Umegawa, Yuichi; Tsuchikawa, Hiroshi; Matsumori, Nobuaki; Seo, Sangjae; Shinoda, Wataru; Murata, Michio.

:: Biophysical Journal, 巻 117, 番号 2, 23.07.2019, p. 307-318.

研究成果: ジャーナルへの寄稿記事

Hanashima, S, Murakami, K, Yura, M, Yano, Y, Umegawa, Y, Tsuchikawa, H, Matsumori, N, Seo, S, Shinoda, W & Murata, M 2019, 'Cholesterol-Induced Conformational Change in the Sphingomyelin Headgroup', Biophysical Journal, 巻. 117, 番号 2, pp. 307-318. https://doi.org/10.1016/j.bpj.2019.06.019
Hanashima S, Murakami K, Yura M, Yano Y, Umegawa Y, Tsuchikawa H その他. Cholesterol-Induced Conformational Change in the Sphingomyelin Headgroup. Biophysical Journal. 2019 7 23;117(2):307-318. https://doi.org/10.1016/j.bpj.2019.06.019
Hanashima, Shinya ; Murakami, Kazuhiro ; Yura, Michihiro ; Yano, Yo ; Umegawa, Yuichi ; Tsuchikawa, Hiroshi ; Matsumori, Nobuaki ; Seo, Sangjae ; Shinoda, Wataru ; Murata, Michio. / Cholesterol-Induced Conformational Change in the Sphingomyelin Headgroup. :: Biophysical Journal. 2019 ; 巻 117, 番号 2. pp. 307-318.
@article{c030d174a50a4112b49f3c1dc22a7c8c,
title = "Cholesterol-Induced Conformational Change in the Sphingomyelin Headgroup",
abstract = "Sphingomyelin (SM) and cholesterol (Cho) are the important lipids for the formation of biologically functional membrane domains, lipid rafts. However, the interaction between Cho and the headgroup of SM remains unclear. In this study, we performed solid-state NMR experiments to reveal the Cho effects on the headgroup conformation using 2H-labeled stearoyl-SM (SSM). Deuterated SSMs at the Cα, Cβ, and Cγ positions of a choline moiety were separately prepared and subjected to NMR measurements to determine the quadrupolar splitting of 2H signals in hydrated SSM unitary and SSM/Cho (1:1) bilayers. Using 2H NMR and 13C-31P REDOR data, the conformation and orientation of the choline moiety were deduced and compared with those derived from molecular dynamics simulations. In SSM unitary bilayers, three torsional angles in the phosphocholine moiety, P-O-Cα-Cβ, were found to be consecutive +gauche(g)/+g/+g or −g/−g/−g. The orientation and conformation of the SSM headgroup were consistent with the results of our molecular dynamics simulations and the previous results on phosphatidylcholines. The quadrupolar coupling at the α methylene group slightly increased in the presence of Cho, and those at the Cβ and Cγ decreased more significantly, thus suggesting that Cho reduced the gauche conformation at the Cα-Cβ torsion. The conformational ensemble in the presence of Cho may enhance the so-called umbrella effect of the SSM headgroup, resulting in the stabilization of Cho near the SM molecules by concealing the hydrophobic Cho core from interfacial water. We also examined the effect of the chiral centers at the sphingosine chain to the headgroup conformation by determining the enantiomeric excess between the diastereomeric +g/+g/+g and −g/−g/−g conformers using (S)-Cα-deuterated and (R)-Cα-deuterated SSMs. Their 2H NMR measurements showed that the chiral centers induced the slight diastereomeric excess in the SM headgroup conformation.",
author = "Shinya Hanashima and Kazuhiro Murakami and Michihiro Yura and Yo Yano and Yuichi Umegawa and Hiroshi Tsuchikawa and Nobuaki Matsumori and Sangjae Seo and Wataru Shinoda and Michio Murata",
year = "2019",
month = "7",
day = "23",
doi = "10.1016/j.bpj.2019.06.019",
language = "English",
volume = "117",
pages = "307--318",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "2",

}

TY - JOUR

T1 - Cholesterol-Induced Conformational Change in the Sphingomyelin Headgroup

AU - Hanashima, Shinya

AU - Murakami, Kazuhiro

AU - Yura, Michihiro

AU - Yano, Yo

AU - Umegawa, Yuichi

AU - Tsuchikawa, Hiroshi

AU - Matsumori, Nobuaki

AU - Seo, Sangjae

AU - Shinoda, Wataru

AU - Murata, Michio

PY - 2019/7/23

Y1 - 2019/7/23

N2 - Sphingomyelin (SM) and cholesterol (Cho) are the important lipids for the formation of biologically functional membrane domains, lipid rafts. However, the interaction between Cho and the headgroup of SM remains unclear. In this study, we performed solid-state NMR experiments to reveal the Cho effects on the headgroup conformation using 2H-labeled stearoyl-SM (SSM). Deuterated SSMs at the Cα, Cβ, and Cγ positions of a choline moiety were separately prepared and subjected to NMR measurements to determine the quadrupolar splitting of 2H signals in hydrated SSM unitary and SSM/Cho (1:1) bilayers. Using 2H NMR and 13C-31P REDOR data, the conformation and orientation of the choline moiety were deduced and compared with those derived from molecular dynamics simulations. In SSM unitary bilayers, three torsional angles in the phosphocholine moiety, P-O-Cα-Cβ, were found to be consecutive +gauche(g)/+g/+g or −g/−g/−g. The orientation and conformation of the SSM headgroup were consistent with the results of our molecular dynamics simulations and the previous results on phosphatidylcholines. The quadrupolar coupling at the α methylene group slightly increased in the presence of Cho, and those at the Cβ and Cγ decreased more significantly, thus suggesting that Cho reduced the gauche conformation at the Cα-Cβ torsion. The conformational ensemble in the presence of Cho may enhance the so-called umbrella effect of the SSM headgroup, resulting in the stabilization of Cho near the SM molecules by concealing the hydrophobic Cho core from interfacial water. We also examined the effect of the chiral centers at the sphingosine chain to the headgroup conformation by determining the enantiomeric excess between the diastereomeric +g/+g/+g and −g/−g/−g conformers using (S)-Cα-deuterated and (R)-Cα-deuterated SSMs. Their 2H NMR measurements showed that the chiral centers induced the slight diastereomeric excess in the SM headgroup conformation.

AB - Sphingomyelin (SM) and cholesterol (Cho) are the important lipids for the formation of biologically functional membrane domains, lipid rafts. However, the interaction between Cho and the headgroup of SM remains unclear. In this study, we performed solid-state NMR experiments to reveal the Cho effects on the headgroup conformation using 2H-labeled stearoyl-SM (SSM). Deuterated SSMs at the Cα, Cβ, and Cγ positions of a choline moiety were separately prepared and subjected to NMR measurements to determine the quadrupolar splitting of 2H signals in hydrated SSM unitary and SSM/Cho (1:1) bilayers. Using 2H NMR and 13C-31P REDOR data, the conformation and orientation of the choline moiety were deduced and compared with those derived from molecular dynamics simulations. In SSM unitary bilayers, three torsional angles in the phosphocholine moiety, P-O-Cα-Cβ, were found to be consecutive +gauche(g)/+g/+g or −g/−g/−g. The orientation and conformation of the SSM headgroup were consistent with the results of our molecular dynamics simulations and the previous results on phosphatidylcholines. The quadrupolar coupling at the α methylene group slightly increased in the presence of Cho, and those at the Cβ and Cγ decreased more significantly, thus suggesting that Cho reduced the gauche conformation at the Cα-Cβ torsion. The conformational ensemble in the presence of Cho may enhance the so-called umbrella effect of the SSM headgroup, resulting in the stabilization of Cho near the SM molecules by concealing the hydrophobic Cho core from interfacial water. We also examined the effect of the chiral centers at the sphingosine chain to the headgroup conformation by determining the enantiomeric excess between the diastereomeric +g/+g/+g and −g/−g/−g conformers using (S)-Cα-deuterated and (R)-Cα-deuterated SSMs. Their 2H NMR measurements showed that the chiral centers induced the slight diastereomeric excess in the SM headgroup conformation.

UR - http://www.scopus.com/inward/record.url?scp=85068699419&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068699419&partnerID=8YFLogxK

U2 - 10.1016/j.bpj.2019.06.019

DO - 10.1016/j.bpj.2019.06.019

M3 - Article

VL - 117

SP - 307

EP - 318

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 2

ER -