|
KMID : 0620920070390050594
|
|
Experimental & Molecular Medicine
2007 Volume.39 No. 5 p.594 ~ p.602
|
|
|
Homo-dimerization of RyR1 C-terminus via charged residues in random coils or in an α-helix
|
|
Lee Eun-Hui
Allen Paul D.
|
|
|
Abstract
|
|
|
|
To investigate the mechanism by which the C-terminus (4,938-5,037) of the ryanodine receptor 1 (RyR1) homo- tetramerizes, forming a functional Ca2+-release channel, the structural requirements for the tetramerization were studied using site-directed mutagenesis. Alanine-substitutions at five charged residues, E4976, H5003, D5026, E5033 and D5034, significantly decreased the formation of homo-dimers (reduced by ＞ 50%). Interaction between the C-terminus and cytoplasmic loop I (4,821-4,835) required two positively charged residues, H4832 and K4835. Based on the predicted protein secondary structures, all seven charged residues are located in random coils. Paired alanine- 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 homo- tetramerization of RyR1 may be mediated by intraand/ or inter-monomer electrostatic interactions among the C-terminal charged residues in random coils or in an α -helix.
|
|
|
KEYWORD
|
|
|
mutagenesis, site-directed, ryanodine receptor release channel, structure-activity relationship
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
    
|
|