Figure 4. The intra- and inter-domain contacts of the RyR1 channel domain may contribute to channel gating.
a, VSC and CTD mediate the interactions between the channel domain and the Central domain in the cytoplasmic region of RyR1. Shown in the inset is a circle formed by the cytoplasmic fragment of S6, CTD, and VSC that provides the primary accommodation site for the Central domain. Only one protomer is domain-colored, and the other three protomers are shown in light to dark grey in semi-transparent surface view. b, Analysis of the interactions between the channel domain and the Central domain. The green circles in the right panel indicate the interfaces between the Central domain and the channel domain. Detailed interactions can be found in Extended Data Fig. 10. c, The EF-hand sub-domain in the Central domain contacts VSC and may provide the molecular basis for Ca2+-mediated modulation of RyR1. A semi-transparent surface is shown for the EF-hand sub-domain. The potential interface is highlighted by the orange circle. d, Putative conformational changes of the S6 segments may result in the opening of the activation gate. e, A cartoon diagram to illustrate the actions from the surrounding domains and structural segments that may lead to conformational changes of S6. f, A cartoon illustration of the complex interactions among the different domains of RyR1. Each arrow denotes two mutually interacting domains. Single-headed arrows indicate the directions of allosteric changes, whereas double-headed arrows suggest two-way flow of conformational changes.