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. 2003 Dec 15;376(Pt 3):795–799. doi: 10.1042/BJ20030597

Oligomerization of the cardiac ryanodine receptor C-terminal tail.

Richard Stewart 1, Spyros Zissimopoulos 1, F Anthony Lai 1
PMCID: PMC1223808  PMID: 12959641

Abstract

The C-terminal 100 amino acids of the RyR (ryanodine receptor), referred to as the C-terminal tail, is a highly conserved sequence that is present in all known RyR isoforms and which has been implicated in channel function. Deleting the final 15 amino acids from the full-length skeletal muscle RyR resulted in an inactive channel, attributed to impaired assembly of a tetrameric RyR complex [Gao, Tripathy, Lu and Meissner (1997) FEBS Lett. 412, 223-226]. To account for these observations, the C-terminal tail itself may be an important molecular determinant of oligomerization. Alternatively, the large N-terminal cytoplasmic domain may fold back upon itself to interact with the C-terminal tail to provide a correctly folded tetrameric structure. We explored these possibilities for RyR2 (cardiac RyR) using the yeast two-hybrid interaction assay and in vitro translation followed by immunoprecipitation and chemical cross-linking. The data indicate that the C-terminal tail of RyR2 is capable of self-tetramerization. Moreover, a truncated C-terminal tail, lacking the final 15 amino acids, failed to self-associate. These observations suggest that the intrinsic ability of the RyR C-terminal tail to self-tetramerize may be vitally important for the oligomeric assembly of the native RyR channel.

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Selected References

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  1. Bhat M. B., Zhao J., Takeshima H., Ma J. Functional calcium release channel formed by the carboxyl-terminal portion of ryanodine receptor. Biophys J. 1997 Sep;73(3):1329–1336. doi: 10.1016/S0006-3495(97)78166-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chen S. R., Airey J. A., MacLennan D. H. Positioning of major tryptic fragments in the Ca2+ release channel (ryanodine receptor) resulting from partial digestion of rabbit skeletal muscle sarcoplasmic reticulum. J Biol Chem. 1993 Oct 25;268(30):22642–22649. [PubMed] [Google Scholar]
  3. Galvan D. L., Borrego-Diaz E., Perez P. J., Mignery G. A. Subunit oligomerization, and topology of the inositol 1,4, 5-trisphosphate receptor. J Biol Chem. 1999 Oct 8;274(41):29483–29492. doi: 10.1074/jbc.274.41.29483. [DOI] [PubMed] [Google Scholar]
  4. Gao L., Tripathy A., Lu X., Meissner G. Evidence for a role of C-terminal amino acid residues in skeletal muscle Ca2+ release channel (ryanodine receptor) function. FEBS Lett. 1997 Jul 21;412(1):223–226. doi: 10.1016/s0014-5793(97)00781-3. [DOI] [PubMed] [Google Scholar]
  5. Grunwald R., Meissner G. Lumenal sites and C terminus accessibility of the skeletal muscle calcium release channel (ryanodine receptor). J Biol Chem. 1995 May 12;270(19):11338–11347. doi: 10.1074/jbc.270.19.11338. [DOI] [PubMed] [Google Scholar]
  6. Lai F. A., Erickson H. P., Rousseau E., Liu Q. Y., Meissner G. Purification and reconstitution of the calcium release channel from skeletal muscle. Nature. 1988 Jan 28;331(6154):315–319. doi: 10.1038/331315a0. [DOI] [PubMed] [Google Scholar]
  7. Lai F. A., Misra M., Xu L., Smith H. A., Meissner G. The ryanodine receptor-Ca2+ release channel complex of skeletal muscle sarcoplasmic reticulum. Evidence for a cooperatively coupled, negatively charged homotetramer. J Biol Chem. 1989 Oct 5;264(28):16776–16785. [PubMed] [Google Scholar]
  8. Maeda N., Kawasaki T., Nakade S., Yokota N., Taguchi T., Kasai M., Mikoshiba K. Structural and functional characterization of inositol 1,4,5-trisphosphate receptor channel from mouse cerebellum. J Biol Chem. 1991 Jan 15;266(2):1109–1116. [PubMed] [Google Scholar]
  9. Magnino F., Schmidt K., Mery L., Dufour J. F. Rat inositol 1,4,5-trisphosphate receptor isoform 2 interacts with itself in its C-terminal portion and upstream of the first transmembrane domain. Eur J Biochem. 2001 Nov;268(22):5981–5988. doi: 10.1046/j.0014-2956.2001.02559.x. [DOI] [PubMed] [Google Scholar]
  10. Marty I., Villaz M., Arlaud G., Bally I., Ronjat M. Transmembrane orientation of the N-terminal and C-terminal ends of the ryanodine receptor in the sarcoplasmic reticulum of rabbit skeletal muscle. Biochem J. 1994 Mar 15;298(Pt 3):743–749. doi: 10.1042/bj2980743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mignery G. A., Newton C. L., Archer B. T., 3rd, Südhof T. C. Structure and expression of the rat inositol 1,4,5-trisphosphate receptor. J Biol Chem. 1990 Jul 25;265(21):12679–12685. [PubMed] [Google Scholar]
  12. Mignery G. A., Südhof T. C. The ligand binding site and transduction mechanism in the inositol-1,4,5-triphosphate receptor. EMBO J. 1990 Dec;9(12):3893–3898. doi: 10.1002/j.1460-2075.1990.tb07609.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mikoshiba K., Furuichi T., Miyawaki A. Structure and function of IP3 receptors. Semin Cell Biol. 1994 Aug;5(4):273–281. doi: 10.1006/scel.1994.1033. [DOI] [PubMed] [Google Scholar]
  14. Pfaffinger P. J., DeRubeis D. Shaker K+ channel T1 domain self-tetramerizes to a stable structure. J Biol Chem. 1995 Dec 1;270(48):28595–28600. doi: 10.1074/jbc.270.48.28595. [DOI] [PubMed] [Google Scholar]
  15. Sayers L. G., Miyawaki A., Muto A., Takeshita H., Yamamoto A., Michikawa T., Furuichi T., Mikoshiba K. Intracellular targeting and homotetramer formation of a truncated inositol 1,4,5-trisphosphate receptor-green fluorescent protein chimera in Xenopus laevis oocytes: evidence for the involvement of the transmembrane spanning domain in endoplasmic reticulum targeting and homotetramer complex formation. Biochem J. 1997 Apr 1;323(Pt 1):273–280. doi: 10.1042/bj3230273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Tunwell R. E., Wickenden C., Bertrand B. M., Shevchenko V. I., Walsh M. B., Allen P. D., Lai F. A. The human cardiac muscle ryanodine receptor-calcium release channel: identification, primary structure and topological analysis. Biochem J. 1996 Sep 1;318(Pt 2):477–487. doi: 10.1042/bj3180477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Zorzato F., Fujii J., Otsu K., Phillips M., Green N. M., Lai F. A., Meissner G., MacLennan D. H. Molecular cloning of cDNA encoding human and rabbit forms of the Ca2+ release channel (ryanodine receptor) of skeletal muscle sarcoplasmic reticulum. J Biol Chem. 1990 Feb 5;265(4):2244–2256. [PubMed] [Google Scholar]

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