Presentation of membrane-anchored glycosphingolipids determined from molecular dynamics simulations and NMR paramagnetic relaxation rate enhancement

Mari L. DeMarco, Robert J. Woods, James H. Prestegard, Fang Tian

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Challenges for structural characterization of membrane-bound glycosphingolipids include their high internal dynamic motions and their physical proximity to membrane surfaces. Here we demonstrate that NMR paramagnetic relaxation enhancement can be used, alongside independent molecular dynamics simulations and an outer-sphere relaxation model, to quantitatively characterize the presentation (insertion depth and orientation relative to a membrane surface) of ganglioside GM1 in biologically relevant membrane environments. Longitudinal and transverse paramagnetic relaxation enhancement effects were measured for GM1, anchored to phospholipid bicelles, using both water-soluble and membrane-anchored paramagnetic probes, respectively. A method was developed to rapidly calculate paramagnetic relaxation enhancement effects from thousands of structures taken from a simulation of GM1 in a phospholipid bilayer. The combined computational and experimental approach yielded experimentally verified atomic-resolution 3D models of a highly plastic membrane-bound biomolecule.

Original languageEnglish (US)
Pages (from-to)1334-1338
Number of pages5
JournalJournal of the American Chemical Society
Volume132
Issue number4
DOIs
StatePublished - Feb 3 2010

Fingerprint

Glycosphingolipids
Molecular Dynamics Simulation
Molecular dynamics
Nuclear magnetic resonance
Membranes
Computer simulation
Phospholipids
G(M1) Ganglioside
Biomolecules
Plastics
Water

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

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Presentation of membrane-anchored glycosphingolipids determined from molecular dynamics simulations and NMR paramagnetic relaxation rate enhancement. / DeMarco, Mari L.; Woods, Robert J.; Prestegard, James H.; Tian, Fang.

In: Journal of the American Chemical Society, Vol. 132, No. 4, 03.02.2010, p. 1334-1338.

Research output: Contribution to journalArticle

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