(A) Proposed transmembrane
arrangements for the RyR showing two possible orientations for the
luminal loop between M3 and M4. If this loop is located in the lumen,
it may be a site of interaction with triadin, and by extension with
calsequestrin. Conversely, if the loop dips back into the membrane, it
may form either a part of the conduction pathway or ion selectivity
filter. (B) Sequence comparison of the proposed pore region.
The sequence for the loop between M3 and M4 is given for the human
skeletal RyR1 isoform, as well as the residues that are conserved
between RyR subtypes, the conserved sequence for the related
IP3Rs, locations for amino acids that are identical between
all RyR and IP3R subtypes, and the analogous residues in
the selectivity filter of the S. lividans K+
channel.