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Intrinsic lattice formation by the ryanodine receptor calcium-release channel

Nature Cell Biology volume 2, pages 669–671 (2000)Cite this article

Abstract

Recent theoretical analysis of a model lattice of interacting transmembrane receptor proteins has indicated that such clustering in the membrane could provide a novel mechanism for regulating receptor signalling in cells1,2. It has been calculated that cooperative interactions between receptors organized into a cluster, or array, in the membrane would dramatically increase their sensitivity to activation by ligand1,2. Sensitivity to ligand would increase with the extent of spread of activity within the receptor lattice. Hence, formation of extensive receptor lattices in the membrane would allow a large population of receptors to be simultaneously switched on, or off, by a very small change in ligand concentration. We show here that lattice formation is an intrinsic property of an integral membrane protein, the ryanodine-sensitive calcium-release channel (RyR) of endoplasmic reticulum. The purified protein spontaneously assembled into two-dimensional lattices in solution, enabling the construction of a 25 Å projection map that identifies the mode of interaction between RyR oligomers. Our observations on the RyR provide a new perspective on various properties of cell signalling via this and other receptors.

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Figure 1: Two-dimensional lattices formed by purified RyR.
Figure 2: Two-dimensional lattices of RyR formed at various protein concentrations.

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Acknowledgements

We thank N. Unwin, R. Henderson and D. Trentham for helpful discussions and encouragement, and the British Heart Foundation for grant support.

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Author notes

  1. Chang Cheng Yin

    Present address: Department of Crystallography, Birkbeck College, London, WC1E 7HX, UK

Authors and Affiliations

  1. Department of Cardiology, Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, UK

    Chang Cheng Yin & F. Anthony Lai

  2. MRC National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK

    Chang Cheng Yin & F. Anthony Lai

Authors
  1. Chang Cheng Yin
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  2. F. Anthony Lai
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Correspondence to F. Anthony Lai.

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Yin, C., Lai, F. Intrinsic lattice formation by the ryanodine receptor calcium-release channel. Nat Cell Biol 2, 669–671 (2000). https://doi.org/10.1038/35023625

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