Structural studies of inositol 1,4,5-trisphosphate receptor: Coupling ligand binding to channel gating

Jenny Chan, Haruka Yamazaki, Noboru Ishiyama, Min Duk Seo, Tapas K. Mal, Takayuki Michikawa, Katsuhiko Mikoshiba, Mitsuhiko Ikura

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45 Scopus citations


The three isoforms of the inositol 1,4,5-trisphosphate receptor (IP 3R) exhibit distinct IP3 sensitivities and cooperativities in calcium (Ca2+) channel function. The determinants underlying this isoform-specific channel gating mechanism have been localized to the N-terminal suppressor region of IP3R. We determined the 1.9 Å crystal structure of the suppressor domain from type 3 IP3R (IP 3R3SUP, amino acids 1-224) and revealed structural features contributing to isoform-specific functionality of IP3R by comparing it with our previously determined structure of the type 1 suppressor domain (IP3R1SUP). The molecular surface known to associate with the ligand binding domain (amino acids 224-604) showed marked differences between IP3R3SUP and IP3R1 SUP. Our NMR and biochemical studies showed that three spatially clustered residues (Glu-20, Tyr-167, and Ser-217 in IP3R1 and Glu-19, Trp-168, and Ser-218 in IP3R3) within the N-terminal suppressor domains of IP3R1SUP and IP3R3SUP interact directly with their respective C-terminal fragments. Together with the accompanying paper (Yamazaki, H., Chan, J., Ikura, M., Michikawa, T., and Mikoshiba, K. (2010) J. Biol. Chem. 285, 36081-36091), we demonstrate that the single aromatic residue in this region (Tyr-167 in IP3R1 and Trp-168 in IP3R3) plays a critical role in the coupling between ligand binding and channel gating.

Original languageEnglish (US)
Pages (from-to)36092-36099
Number of pages8
JournalJournal of Biological Chemistry
Issue number46
StatePublished - Nov 12 2010

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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