By X. Wehrens, A. Marks
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Extra resources for Arrhythmias and sudden death in athletes
67 Thus the entire molecule contains 8 TM sequences in 4 TM hairpin loops, but only 3 of these TM hairpins are required for release channel function. IDENTITY OF TM SEQUENCES RyR release channel molecules are homotetramers of 2,350,000 Da, formed from four monomers, each of 565 kDa. 9. These four sequences: aa and were designated M1 to M4 and were proposed to form two hairpin loops in the topological model proposed by Takeshima et al. 70 With the view that TM sequences in pumps and channels might require charged residues in TM sequences, the criteria for prediction of a TM sequence were made less stringent.
And were considered to be very tentative; the others were: and M1, M2, M3 and M4 in the Takeshima model correspond to M5, M6, M8 and M10 in the Zorzato model. 4 However, the sequences of M3 and M4 were not well conserved and the hydrophobicity of M4 could clearly be extended to over 40 aa. The sequencing of RyR3,12 however, led to a different pattern. In RyR3, the sequence corresponding to M3 was not hydrophobic and could not be TM, but the possibility now existed that M4 alone might be long enough to form a hairpin helix.
The identity of these segments is covered in Chapter 4 of this book. The focus of this chapter is the question of which parts of the ryanodine receptor form the TM domain. We conclude that there are six essential TM segments which lie between amino acids (aa) 4557 and 4935. They include three TM hairpin loops and a selectivity filter which is located within the final hairpin loop between aa 4854 and 4911. We also conclude that RyR contains an additional upstream TM hairpin loop which is contained within a single contiguous hydrophobic sequence between aa 4323 and 4363 and is preceded by a very basic sequence of about 19 aa which lies in the cytosol.
Arrhythmias and sudden death in athletes by X. Wehrens, A. Marks
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