High resolution

Module 3: Figure InsP3R activation

Proposed activation of the inositol 1,4,5-trisphosphate receptor (InsP3R) by the co-operative action of InsP3 and Ca2+.

In this figure, two of the channel subunits (coloured red and blue) that make up the tetramer are shown with their pore regions coming together to form the channel. In the resting state (shown on the left), the pore may be held in a closed state by the N-terminal region of one receptor interacting with the C-terminal region of a neighbouring receptor. Upon binding first InsP3 and then Ca2+, there is a marked conformational change that removes this N-terminal/C-terminal interaction and the gate region opens to allow Ca2+ to flow out of the endoplasmic reticulum (ER) into the cytoplasm. This drawing is based on a model shown in Figure 5 of Taylor et al. 2004. Reproduced from Trends Biochem. Sci., Vol. 29, Taylor, C.W., da Fonseca, P.C.A. and Morris, E.P., IP3 receptors: the search for structure, pages 210–219. Copyright (2004), with permission from Elsevier. The position of the luminal Ca2+ sensor (indicated by an asterisk) is postulated to lie close to the helix bundle crossing region that constitutes the gate, based on information in Chen et al. (2014).