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Cholesterol modulates glycolipid conformation and receptor activity

Abstract

We document a new dimension of surface recognition in which communication is controlled through the collective behavior of lipids. Membrane cholesterol induces a tilt in glycolipid receptor headgroup, resulting in loss of access for ligand binding. This property appears to organize erythrocyte blood group presentation and glycolipid receptor function during the activation of sperm fertility, suggesting that lipid 'allostery' is a means to regulate membrane recognition processes.

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Figure 1: Cholesterol alters GSL surface recognition in human tissue and blood group presentation in human erythrocyte membrane.
Figure 2: Cholesterol depletion during capacitation enhances GSL recognition in the plasma membrane of mouse sperm.

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Acknowledgements

The authors thank I. Nuesslein, M. Gerl, I. Levental, H. Kaiser (Max Planck Institute for Molecular Cell Biology and Genetics), K. Hölig (Technische Univesität), P. Paroutis, M. Woodside (Hospital for Sick Children), U. Devi, W. Jones and M. Swann (Farfield Sensors) for their assistance in this project. This work was supported by a MPI-CBG stipend (D.L.) and funding to K.S. (EU FP6 Lipid PRISM Grant LSHB-CT2007-037740, DFG Schwerpunktprogramm 1175 Grant SI459/2-1, DFG Transregio 83 Grant: TRR83 TP02, BMBF ForMaT Grant: 03FO1212, ESF “LIPIDPROD” Grant: SI459/3-1); I.V. (Academy of Finland); and funding to C.A.L. (Canadian Institutes of Health Research Grant MT 13747, Ontario HIV Treatment Network and Canfar support).

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Membrane and sperm recognition experiments were performed by D.L.; histology was by B.B.; molecular dynamics simulations were by T.R. and I.V.; DPI was performed by D.L., M.G. and U.C.; D.L., C.A.L. and K.S. formulated the project and wrote the manuscript.

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Correspondence to Kai Simons.

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The authors declare no competing financial interests.

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Supplementary Methods and Supplementary Figures 1–10 (PDF 1001 kb)

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Lingwood, D., Binnington, B., Róg, T. et al. Cholesterol modulates glycolipid conformation and receptor activity. Nat Chem Biol 7, 260–262 (2011). https://doi.org/10.1038/nchembio.551

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  • DOI: https://doi.org/10.1038/nchembio.551

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