期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 285, 期 46, 页码 36081-36091出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.140129
关键词
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资金
- Ministry of Education, Science, Sports, and Culture of Japan [20370054, 20220007]
- Canadian Institutes of Health Research
- Heart and Stroke Foundation of Ontario
- Grants-in-Aid for Scientific Research [20370054] Funding Source: KAKEN
The N-terminal similar to 220-amino acid region of the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R)/Ca2+ release channel has been referred to as the suppressor/coupling domain because it is required for both IP3 binding suppression and IP3-induced channel gating. Measurements of IP3-induced Ca2+ fluxes of mutagenized mouse type 1 IP3R (IP(3)R1) showed that the residues responsible for IP3 binding suppression in this domain were not essential for channel opening. On the other hand, a single amino acid substitution of Tyr-167 to alanine completely impaired IP3-induced Ca2+ release without reducing the IP3 binding activity. The corresponding residue in type 3 IP3R (IP3R3), Trp-168, was also critical for channel opening. Limited trypsin digestion experiments showed that the trypsin sensitivities of the C-terminal gatekeeper domain differed markedly between the wild-type channel and the Tyr-167 mutant under the optimal conditions for channel opening. These results strongly suggest that the Tyr/Trp residue (Tyr-167 in IP(3)R1 and Trp-168 in IP3R3) is critical for the functional coupling between IP3 binding and channel gating by maintaining the structural integrity of the C-terminal gatekeeper domain at least under activation gating.
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