Acknowledgement
This work was supported by grants from the National Research Foundation of Korea (NRF-2018R1A5A2025964), EDISON (EDucation-research Integration through Simulation On the Net) Program (NRF-2016M3C1A6936605) and the Korea Health Technology R&D Project, through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant No. HP20C0199). This work was also supported by a grant from the M.D., Ph.D./Medical Scientist Training Programs through KHIDI to Y.K.J. We thank Prof. Chansik Hong for technical advices and helpful discussions.
References
- Al Khamici, H., Hossain, K.R., Cornell, B.A., and Valenzuela, S.M. (2016). Investigating sterol and redox regulation of the ion channel activity of CLIC1 using tethered bilayer membranes. Membranes (Basel) 6, 51. https://doi.org/10.3390/membranes6040051
- Bannister, J.P., Young, B.A., Sivaprasadarao, A., and Wray, D. (1999). Conserved extracellular cysteine residues in the inwardly rectifying potassium channel Kir2.3 are required for function but not expression in the membrane. FEBS Lett. 458, 393-399. https://doi.org/10.1016/S0014-5793(99)01096-0
- Berman, J.M. and Awayda, M.S. (2013). Redox artifacts in electrophysiological recordings. Am. J. Physiol. Cell Physiol. 304, C604-C613. https://doi.org/10.1152/ajpcell.00318.2012
- Calderon-Rivera, A., Andrade, A., Hernandez-Hernandez, O., Gonzalez-Ramirez, R., Sandoval, A., Rivera, M., Gomora, J.C., and Felix, R. (2012). Identification of a disulfide bridge essential for structure and function of the voltage-gated Ca(2+) channel alpha(2)delta-1 auxiliary subunit. Cell Calcium 51, 22-30. https://doi.org/10.1016/j.ceca.2011.10.002
- Chen, C., Calhoun, J.D., Zhang, Y., Lopez-Santiago, L., Zhou, N., Davis, T.H., Salzer, J.L., and Isom, L.L. (2012). Identification of the cysteine residue responsible for disulfide linkage of Na+ channel alpha and beta2 subunits. J. Biol. Chem. 287, 39061-39069. https://doi.org/10.1074/jbc.M112.397646
- Cho, H.C., Tsushima, R.G., Nguyen, T.T., Guy, H.R., and Backx, P.H. (2000). Two critical cysteine residues implicated in disulfide bond formation and proper folding of Kir2.1. Biochemistry 39, 4649-4657. https://doi.org/10.1021/bi992469g
- Choi, W., Clemente, N., Sun, W., Du, J., and Lu, W. (2019). The structures and gating mechanism of human calcium homeostasis modulator 2. Nature 576, 163-167. https://doi.org/10.1038/s41586-019-1781-3
- Demura, K., Kusakizako, T., Shihoya, W., Hiraizumi, M., Nomura, K., Shimada, H., Yamashita, K., Nishizawa, T., Taruno, A., and Nureki, O. (2020). Cryo-EM structures of calcium homeostasis modulator channels in diverse oligomeric assemblies. Sci. Adv. 6, eaba8105. https://doi.org/10.1126/sciadv.aba8105
- Deutsch, C. (2003). The birth of a channel. Neuron 40, 265-276. https://doi.org/10.1016/S0896-6273(03)00506-3
- Dreses-Werringloer, U., Lambert, J.C., Vingtdeux, V., Zhao, H., Vais, H., Siebert, A., Jain, A., Koppel, J., Rovelet-Lecrux, A., Hannequin, D., et al. (2008). A polymorphism in CALHM1 influences Ca2+ homeostasis, Abeta levels, and Alzheimer's disease risk. Cell 133, 1149-1161. https://doi.org/10.1016/j.cell.2008.05.048
- Drozdzyk, K., Sawicka, M., Bahamonde-Santos, M.I., Jonas, Z., Deneka, D., Albrecht, C., and Dutzler, R. (2020). Cryo-EM structures and functional properties of CALHM channels of the human placenta. Elife 9, e55853. https://doi.org/10.7554/elife.55853
- Duan, J., Li, J., Chen, G.L., Ge, Y., Liu, J., Xie, K., Peng, X., Zhou, W., Zhong, J., Zhang, Y., et al. (2019). Cryo-EM structure of TRPC5 at 2.8-A resolution reveals unique and conserved structural elements essential for channel function. Sci. Adv. 5, eaaw7935. https://doi.org/10.1126/sciadv.aaw7935
- Duan, J., Li, J., Zeng, B., Chen, G.L., Peng, X., Zhang, Y., Wang, J., Clapham, D.E., Li, Z., and Zhang, J. (2018). Structure of the mouse TRPC4 ion channel. Nat. Commun. 9, 3102. https://doi.org/10.1038/s41467-018-05247-9
- Foskett, J.K. (2020). Structures of CALHM channels revealed. Nat. Struct. Mol. Biol. 27, 227-228. https://doi.org/10.1038/s41594-020-0391-y
- Fujiwara, Y., Takeshita, K., Nakagawa, A., and Okamura, Y. (2013). Structural characteristics of the redox-sensing coiled coil in the voltage-gated H+ channel. J. Biol. Chem. 288, 17968-17975. https://doi.org/10.1074/jbc.M113.459024
- Gamper, N., Stockand, J.D., and Shapiro, M.S. (2005). The use of Chinese hamster ovary (CHO) cells in the study of ion channels. J. Pharmacol. Toxicol. Methods 51, 177-185. https://doi.org/10.1016/j.vascn.2004.08.008
- Gibson, D.G., Young, L., Chuang, R.Y., Venter, J.C., Hutchison, C.A., 3rd, and Smith, H.O. (2009). Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat. Methods 6, 343-345. https://doi.org/10.1038/nmeth.1318
- Hong, C., Kwak, M., Myeong, J., Ha, K., Wie, J., Jeon, J.H., and So, I. (2015). Extracellular disulfide bridges stabilize TRPC5 dimerization, trafficking, and activity. Pflugers Arch. 467, 703-712. https://doi.org/10.1007/s00424-014-1540-0
- Hwang, E.M., Kim, E., Yarishkin, O., Woo, D.H., Han, K.S., Park, N., Bae, Y., Woo, J., Kim, D., Park, M., et al. (2014). A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes. Nat. Commun. 5, 3227. https://doi.org/10.1038/ncomms4227
- Isacoff, E.Y., Jan, L.Y., and Minor, D.L., Jr. (2013). Conduits of life's spark: a perspective on ion channel research since the birth of neuron. Neuron 80, 658-674. https://doi.org/10.1016/j.neuron.2013.10.040
- Jeon, Y.K., Choi, S.W., Kwon, J.W., Woo, J., Choi, S.W., Kim, S.J., and Kim, S.J. (2021). Thermosensitivity of the voltage-dependent activation of calcium homeostasis modulator 1 (calhm1) ion channel. Biochem. Biophys. Res. Commun. 534, 590-596. https://doi.org/10.1016/j.bbrc.2020.11.035
- Kashio, M., Wei-Qi, G., Ohsaki, Y., Kido, M.A., and Taruno, A. (2019). CALHM1/CALHM3 channel is intrinsically sorted to the basolateral membrane of epithelial cells including taste cells. Sci. Rep. 9, 2681. https://doi.org/10.1038/s41598-019-39593-5
- Ma, Z., Siebert, A.P., Cheung, K.H., Lee, R.J., Johnson, B., Cohen, A.S., Vingtdeux, V., Marambaud, P., and Foskett, J.K. (2012). Calcium homeostasis modulator 1 (CALHM1) is the pore-forming subunit of an ion channel that mediates extracellular Ca2+ regulation of neuronal excitability. Proc. Natl. Acad. Sci. U. S. A. 109, E1963-E1971.
- Ma, Z., Taruno, A., Ohmoto, M., Jyotaki, M., Lim, J.C., Miyazaki, H., Niisato, N., Marunaka, Y., Lee, R.J., Hoff, H., et al. (2018). CALHM3 is essential for rapid ion channel-mediated purinergic neurotransmission of GPCR-mediated tastes. Neuron 98, 547-561.e10. https://doi.org/10.1016/j.neuron.2018.03.043
- Narayan, M. (2012). Disulfide bonds: protein folding and subcellular protein trafficking. FEBS J. 279, 2272-2282. https://doi.org/10.1111/j.1742-4658.2012.08636.x
- Okui, M., Murakami, T., Sun, H., Ikeshita, C., Kanamura, N., and Taruno, A. (2021). Posttranslational regulation of CALHM1/3 channel: N-linked glycosylation and S-palmitoylation. FASEB J. 35, e21527.
- Ramesh, A., Peleh, V., Martinez-Caballero, S., Wollweber, F., Sommer, F., van der Laan, M., Schroda, M., Alexander, R.T., Campo, M.L., and Herrmann, J.M. (2016). A disulfide bond in the TIM23 complex is crucial for voltage gating and mitochondrial protein import. J. Cell Biol. 214, 417-431. https://doi.org/10.1083/jcb.201602074
- Ren, Y., Wen, T., Xi, Z., Li, S., Lu, J., Zhang, X., Yang, X., and Shen, Y. (2020). Cryo-EM structure of the calcium homeostasis modulator 1 channel. Sci. Adv. 6, eaba8161. https://doi.org/10.1126/sciadv.aba8161
- Roh, J.W., Hwang, G.E., Kim, W.K., and Nam, J.H. (2021). Ca2+ sensitivity of anoctamin 6/TMEM16F is regulated by the putative Ca2+-binding reservoir at the N-terminal domain. Mol. Cells 44, 88-100. https://doi.org/10.14348/molcells.2021.2203
- Schulteis, C.T., John, S.A., Huang, Y., Tang, C.Y., and Papazian, D.M. (1995). Conserved cysteine residues in the shaker K+ channel are not linked by a disulfide bond. Biochemistry 34, 1725-1733. https://doi.org/10.1021/bi00005a029
- Schulteis, C.T., Nagaya, N., and Papazian, D.M. (1996). Intersubunit interaction between amino- and carboxyl-terminal cysteine residues in tetrameric shaker K+ channels. Biochemistry 35, 12133-12140. https://doi.org/10.1021/bi961083s
- Syrjanen, J.L., Michalski, K., Chou, T.H., Grant, T., Rao, S., Simorowski, N., Tucker, S.J., Grigorieff, N., and Furukawa, H. (2020). Structure and assembly of calcium homeostasis modulator proteins. Nat. Struct. Mol. Biol. 27, 150-159. https://doi.org/10.1038/s41594-019-0369-9
- Tanis, J.E., Ma, Z., and Foskett, J.K. (2017). The NH2 terminus regulates voltage-dependent gating of CALHM ion channels. Am. J. Physiol. Cell Physiol. 313, C173-C186. https://doi.org/10.1152/ajpcell.00318.2016
- Taruno, A., Vingtdeux, V., Ohmoto, M., Ma, Z., Dvoryanchikov, G., Li, A., Adrien, L., Zhao, H., Leung, S., Abernethy, M., et al. (2013). CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. Nature 495, 223-226. https://doi.org/10.1038/nature11906
- Thompson, J.D., Higgins, D.G., and Gibson, T.J. (1994). CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22, 4673-4680. https://doi.org/10.1093/nar/22.22.4673
- Vingtdeux, V., Chang, E.H., Frattini, S.A., Zhao, H., Chandakkar, P., Adrien, L., Strohl, J.J., Gibson, E.L., Ohmoto, M., Matsumoto, I., et al. (2016). CALHM1 deficiency impairs cerebral neuron activity and memory flexibility in mice. Sci. Rep. 6, 24250. https://doi.org/10.1038/srep24250
- Wang, L., Cvetkov, T.L., Chance, M.R., and Moiseenkova-Bell, V.Y. (2012). Identification of in vivo disulfide conformation of TRPA1 ion channel. J. Biol. Chem. 287, 6169-6176. https://doi.org/10.1074/jbc.M111.329748
- Waterhouse, A., Bertoni, M., Bienert, S., Studer, G., Tauriello, G., Gumienny, R., Heer, F.T., de Beer, T.A.P., Rempfer, C., Bordoli, L., et al. (2018). SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 46(W1), W296-W303. https://doi.org/10.1093/nar/gky427
- Xu, S.Z., Sukumar, P., Zeng, F., Li, J., Jairaman, A., English, A., Naylor, J., Ciurtin, C., Majeed, Y., Milligan, C.J., et al. (2008). TRPC channel activation by extracellular thioredoxin. Nature 451, 69-72. https://doi.org/10.1038/nature06414
- Yang, W., Wang, Y., Guo, J., He, L., Zhou, Y., Zheng, H., Liu, Z., Zhu, P., and Zhang, X.C. (2020). Cryo-electron microscopy structure of CLHM1 ion channel from Caenorhabditis elegans. Protein Sci. 29, 1803-1815. https://doi.org/10.1002/pro.3904
- Yereddi, N.R., Cusdin, F.S., Namadurai, S., Packman, L.C., Monie, T.P., Slavny, P., Clare, J.J., Powell, A.J., and Jackson, A.P. (2013). The immunoglobulin domain of the sodium channel beta3 subunit contains a surface-localized disulfide bond that is required for homophilic binding. FASEB J. 27, 568-580. https://doi.org/10.1096/fj.12-209445
- Zha, X.M., Wang, R., Collier, D.M., Snyder, P.M., Wemmie, J.A., and Welsh, M.J. (2009). Oxidant regulated inter-subunit disulfide bond formation between ASIC1a subunits. Proc. Natl. Acad. Sci. U. S. A. 106, 3573-3578. https://doi.org/10.1073/pnas.0813402106
- Zuniga, L. and Zuniga, R. (2016). Understanding the cap structure in K2P channels. Front. Physiol. 7, 228. https://doi.org/10.3389/fphys.2016.00228