PMID- 31303249
OWN - NLM
STAT- MEDLINE
DCOM- 20200911
LR  - 20200911
IS  - 1542-0086 (Electronic)
IS  - 0006-3495 (Print)
IS  - 0006-3495 (Linking)
VI  - 117
IP  - 2
DP  - 2019 Jul 23
TI  - Cholesterol-Induced Conformational Change in the Sphingomyelin Headgroup.
PG  - 307-318
LID - S0006-3495(19)30508-9 [pii]
LID - 10.1016/j.bpj.2019.06.019 [doi]
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 (2)H-labeled stearoyl-SM (SSM). Deuterated SSMs at 
      the Calpha, Cbeta, and Cgamma positions of a choline moiety were separately prepared and 
      subjected to NMR measurements to determine the quadrupolar splitting of (2)H 
      signals in hydrated SSM unitary and SSM/Cho (1:1) bilayers. Using (2)H NMR and 
      (13)C-(31)P 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-Calpha-Cbeta, 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 alpha methylene group slightly 
      increased in the presence of Cho, and those at the Cbeta and Cgamma decreased more 
      significantly, thus suggesting that Cho reduced the gauche conformation at the 
      Calpha-Cbeta 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)-Calpha-deuterated and 
      (R)-Calpha-deuterated SSMs. Their (2)H NMR measurements showed that the chiral 
      centers induced the slight diastereomeric excess in the SM headgroup 
      conformation.
CI  - Copyright (c) 2019 Biophysical Society. Published by Elsevier Inc. All rights 
      reserved.
FAU - Hanashima, Shinya
AU  - Hanashima S
AD  - Department of Chemistry, Graduate School of Science, Osaka University, Osaka, 
      Japan. Electronic address: hanashimas13@chem.sci.osaka-u.ac.jp.
FAU - Murakami, Kazuhiro
AU  - Murakami K
AD  - Department of Chemistry, Graduate School of Science, Osaka University, Osaka, 
      Japan.
FAU - Yura, Michihiro
AU  - Yura M
AD  - Department of Chemistry, Graduate School of Science, Osaka University, Osaka, 
      Japan.
FAU - Yano, Yo
AU  - Yano Y
AD  - Department of Chemistry, Graduate School of Science, Osaka University, Osaka, 
      Japan.
FAU - Umegawa, Yuichi
AU  - Umegawa Y
AD  - Department of Chemistry, Graduate School of Science, Osaka University, Osaka, 
      Japan; ERATO Lipid Active Structure Project, Japan Science and Technology Agency, 
      Graduate School of Science, Osaka University, Osaka, Japan.
FAU - Tsuchikawa, Hiroshi
AU  - Tsuchikawa H
AD  - Department of Chemistry, Graduate School of Science, Osaka University, Osaka, 
      Japan.
FAU - Matsumori, Nobuaki
AU  - Matsumori N
AD  - Department of Chemistry, Graduate School of Science, Osaka University, Osaka, 
      Japan; Department of Chemistry, Graduate School of Science, Kyushu University, 
      Fukuoka, Japan.
FAU - Seo, Sangjae
AU  - Seo S
AD  - Department of Materials Chemistry, Nagoya University, Nagoya, Japan.
FAU - Shinoda, Wataru
AU  - Shinoda W
AD  - Department of Materials Chemistry, Nagoya University, Nagoya, Japan.
FAU - Murata, Michio
AU  - Murata M
AD  - Department of Chemistry, Graduate School of Science, Osaka University, Osaka, 
      Japan; ERATO Lipid Active Structure Project, Japan Science and Technology Agency, 
      Graduate School of Science, Osaka University, Osaka, Japan. Electronic address: 
      murata@chem.sci.osaka-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190625
PL  - United States
TA  - Biophys J
JT  - Biophysical journal
JID - 0370626
RN  - 0 (Sphingomyelins)
RN  - 0 (Stearic Acids)
RN  - 4ELV7Z65AP (stearic acid)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - AR09D82C7G (Deuterium)
RN  - N91BDP6H0X (Choline)
SB  - IM
MH  - Cholesterol/*pharmacology
MH  - Choline/chemistry
MH  - Deuterium/chemistry
MH  - Magnetic Resonance Spectroscopy
MH  - *Molecular Conformation
MH  - Molecular Dynamics Simulation
MH  - Probability
MH  - Sphingomyelins/*chemistry
MH  - Stearic Acids/chemistry
MH  - Temperature
PMC - PMC6701000
EDAT- 2019/07/16 06:00
MHDA- 2020/09/12 06:00
PMCR- 2020/07/23
CRDT- 2019/07/16 06:00
PHST- 2018/11/27 00:00 [received]
PHST- 2019/06/07 00:00 [revised]
PHST- 2019/06/17 00:00 [accepted]
PHST- 2019/07/16 06:00 [pubmed]
PHST- 2020/09/12 06:00 [medline]
PHST- 2019/07/16 06:00 [entrez]
PHST- 2020/07/23 00:00 [pmc-release]
AID - S0006-3495(19)30508-9 [pii]
AID - 10.1016/j.bpj.2019.06.019 [doi]
PST - ppublish
SO  - Biophys J. 2019 Jul 23;117(2):307-318. doi: 10.1016/j.bpj.2019.06.019. Epub 2019 
      Jun 25.