Homo-dimerization of RyR1 C-terminus via charged residues inrandom coils or in an α-helix

다국어 초록 (Multilingual Abstract)

To investigate the mechanism by which the C-terminus (4,938-5,037) of the ryanodine receptor 1 (RyR1) ho-mo-tetramerizes, forming a functional Ca2+-release channel, the structural requirements for the tetrameri-zation were studied using site-directed mutagenesis. H5003, D5026, E5033 and D5034, significantly de-creased the formation of homo-dimers (reduced by ＞ 50%). Interaction between the C-terminus and cyto-plasmic loop I (4,821-4,835) required two positively charged residues, H4832 and K4835. Based on the pre-dicted protein secondary structures, all seven charged residues are located in random coils. Paired ala-nine-substitutions at six negatively charged residues (E4942A/D4953A, D4945A/E4952A and E4948A/ E4955A) of the α-helix (4,940-4,956) in the C-terminus increased homo-dimerization. Therefore, the ho-mo-tetramerization of RyR1 may be mediated by intra- and/or inter-monomer electrostatic interactions among the C-terminal charged residues in random coils or in an α-helix.

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