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

Hui Lee Eun, Paul D. Allen

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 Ca 2+-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 intra-and/or inter-monomer electrostatic interactions among the C-terminal charged residues in random coils or in an α-helix.

Original languageEnglish (US)
Pages (from-to)594-602
Number of pages9
JournalExperimental and Molecular Medicine
Volume39
Issue number5
StatePublished - Oct 31 2007
Externally publishedYes

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Ryanodine Receptor Calcium Release Channel
Dimerization
Hominidae
Alanine
Substitution reactions
Secondary Protein Structure
Mutagenesis
Site-Directed Mutagenesis
Coulomb interactions
Static Electricity
Dimers
Monomers
Proteins

Keywords

  • Mutagenesis, site-directed
  • Ryanodine receptor calcium release channel
  • Structure-activity relationship

ASJC Scopus subject areas

  • Biochemistry
  • Genetics

Cite this

Homo-dimerization of RyR1 C-terminus via charged residues in random coils or in an α-helix. / Eun, Hui Lee; Allen, Paul D.

In: Experimental and Molecular Medicine, Vol. 39, No. 5, 31.10.2007, p. 594-602.

Research output: Contribution to journalArticle

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