Intrinsic lattice formation by the ryanodine receptor calcium-release channel

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.