TY - JOUR
T1 - Structural studies of inositol 1,4,5-trisphosphate receptor
T2 - Coupling ligand binding to channel gating
AU - Chan, Jenny
AU - Yamazaki, Haruka
AU - Ishiyama, Noboru
AU - Seo, Min Duk
AU - Mal, Tapas K.
AU - Michikawa, Takayuki
AU - Mikoshiba, Katsuhiko
AU - Ikura, Mitsuhiko
PY - 2010/11/12
Y1 - 2010/11/12
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M110.140160
DO - 10.1074/jbc.M110.140160
M3 - Article
C2 - 20843799
AN - SCOPUS:78149243699
SN - 0021-9258
VL - 285
SP - 36092
EP - 36099
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 46
ER -