β-Glucosylation of cholesterol reduces sterol-sphingomyelin interactions

Shinya Hanashima, Nanami Fukuda, Raymond Malabed, Michio Murata, Msanao Kinoshita, Peter Greimel, Yoshio Hirabayashi

研究成果: Contribution to journalArticle査読

抄録

Cholesteryl-β-D-glucoside (ChoGlc) is a mammalian glycolipid that is expressed in brain tissue. The effects of glucosylation on the ordering and lipid interactions of cholesterol (Cho) were examined in membranes composed of N-stearoyl sphingomyelin (SSM), which is abundant in the brain, and to investigate the possible molecular mechanism involved in these interactions. Differential scanning calorimetry revealed that ChoGlc was miscible with SSM in a similar extent of Cho. Solid-state 2H NMR of deuterated SSM and fluorescent anisotropy using 1,6-diphenylhexatriene demonstrated that the glucosylation of Cho significantly reduced the effect of the sterol tetracyclic core on the ordering of SSM chains. The orientation of the sterol core was further examined by solid-state NMR analysis of deuterated and fluorinated ChoGlc analogues. ChoGlc had a smaller tilt angle between the long molecular axis (C3–C17) and the membrane normal than Cho in SSM bilayers, and the fluctuations in the tilt angle were largely unaffected by temperature-dependent mobility changes of SSM acyl chains. This orientation of the sterol core of ChoGlc leads to reduce sterol-SSM interactions. The MD simulation results suggested that the Glc moiety perturbs the SSM-sterol interactions, which reduces the umbrella effect of the phosphocholine headgroup because the hydrophilic glucose moiety resides at the same depth as an SSM amide group. These differences between ChoGlc and Cho also weaken the SSM-ChoGlc interactions. Thus, the distribution and localization of Cho and ChoGlc possibly control the stability of sphingomyelin-based domains that transiently occur at specific locations in biological membranes.

本文言語英語
論文番号183496
ジャーナルBiochimica et Biophysica Acta - Biomembranes
1863
2
DOI
出版ステータス出版済み - 2 1 2021

All Science Journal Classification (ASJC) codes

  • 生物理学
  • 生化学
  • 細胞生物学

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