Self-organizing of RyR1 in native membranes. (A) Slice of an average of subtomograms showing paired tetramers in ultrathin frozen lamellae of rat skeletal muscle. Scale bar, 20 nm. (B) Averaged map of dimeric RyR1 tetramers in situ, showing both T tubule and SR membrane. A near-atomic model of RyR1-FKBP12 is fitted into the map. (C) Enlargement of the contact site in panel E, with nearest residues Lys³¹¹⁵ and Leu³¹¹³ indicated. Gly³¹⁹², in red, is a reported site for a mutation associated with premature death in two patients. (D) Initial and near-final frames of a trajectory movie of a coarse-grained MD simulation of RyR1s in the open state. Residues ranging from 2951 to 3240 are shown in red. Note that the contact sites are located immediately to the right of every corner, in contrast to the “left-handedness” of RyR2–RyR2 contacts noted with Figs. 5 and 8. Images are reproduced with minimal annotation changes in panels from Fig. 3 and frames from Supplemental Movie 4 in Xu et al. (2024). Shared by courtesy of Guohui Li, Yun Zhu, and Fei Sun. Fig. 7 is reprinted with permission from The American Association for the Advancement of Science.