Pairwise contacts of cardiac RyRs. Transmission electron microscopy averages of RyR2 from pigs’ hearts, purified, incubated in 100 μM Ca²⁺, and negatively stained. (A) Averages of contacting pairs (selected by techniques that exclude chance proximity), classified in five groups and aligned on one member. CTS—center to side. The subindex (f or r) distinguishes a rigid and a flexible association mode, the latter evident in the fuzziness of the nonaligned member of the pair. (B) Near-atomic model of the oblique interaction (structure includes FKBP12). Note that in this view from the cytosolic side, the interaction RyR2–RyR2 is left-handed (compare with RyR1–RyR1 interactions in Fig. 4 and 7). (C and D) Enlargement of the boxed region in B, indicating the antiparallel contacts between domains P1 (or Repeat 12), SPRY1, and FKBP12. (E) Diagram of a hypothetical array, built exclusively on the basis of the oblique interaction, which requires alternation between rows with mutual tilts of 12°. Panels from Fig. 2 and 4 in Cabra et al. (2016), reproduced by courtesy of Montserrat Samsó. Fig. 8 is reprinted with permission from Elsevier.