Fig. 1

Triadin 1 interactions with RyR2 and Casq2 proteins. a Schematic representation of Triadin 1 in relation to sarcoplasmic reticulum (SR) membrane. The cytoplasmic amino terminal is followed by a transmembrane segment, then intracellular segment of the protein. The latter includes the “KEKE” (Lysine-Glutamate-Lysine-Glutamate) motif that interacts with RyR2 and Casq2 proteins. bi Schematic representation of junctional sarcoplasmic reticulum (SR) in relation to surface membrane. The L type Ca channel in the sarcolemmal membrane is juxtaposed to the RyR2. Vertical arrow denotes the direction of Ca²⁺ flux (influx) through the L type channel. The RyR2 is embedded in the junctional SR membrane. Vertical arrow denotes the direction of Ca²⁺ flux (efflux) from the SR through the RyR2. Triadin-1 is shown to the right of the RyR2. Transmembrane and KEKE domains are shown in black. In ‘A’ the KEKE domain is shown interacting with the RyR2 channel and with Casq2 proteins (shown as open pentagons). bii Schematic representations of similar structures to those in ‘A’, with one difference. Triadin-1 is now shown as a truncated protein, lacking the KEKE domain (and distal protein). In consequence, triadin-1 can no longer interact with the RyR2 or Casq2 proteins. Diagonal dashed lines indicate that mutations that result in premature stop codons in cytoplasmic, transmembrane or internal segments, upstream of the KEKE motif, can be expected to result in nonfunctional protein