Cryo-EM structures of human calcium homeostasis modulator 5

Structure coordinates and cryo-EM density maps of CALHM5 in the presence of EDTA, Ca2+ and rubidium red have been deposited in the protein data bank under accession numbers 7D61, 7D65, 7D60 and EMD-30587, EMD-30589, EMD-30586, respectively. Ma, Z. et al. CALHM3 is essential for rapid ion channel-mediated purinergic neurotransmission of GPCR-mediated tastes. Neuron 98, 547–561 (2018). CAS Article PubMed PubMed Central Google Scholar Taruno, A. et al. CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. Nature 495, 223–226 (2013). CAS Article PubMed PubMed Central Google Scholar Ma, Z. et al. 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. USA 109, E1963–E1971 (2012). Jun, M. et al. Calhm2 governs astrocytic ATP releasing in the development of depression-like behaviors. Mol. Psychiatry 23, 883–891 (2018). Article Google Scholar Dreses-Werringloer, U. et al. A polymorphism in CALHM1 influences Ca2+ homeostasis, Abeta levels, and Alzheimer’s disease risk. Cell 133, 1149–1161 (2008). CAS Article PubMed PubMed Central Google Scholar Calero, O. et al. Genetic variability of the gene cluster CALHM 1-3 in sporadic Creutzfeldt-Jakob disease. Prion 6, 407–412 (2012). CAS Article PubMed PubMed Central Google Scholar Shibata, N. et al. Genetic association between CALHM1, 2 and 3 polymorphisms and Alzheimer’s disease in a Japanese population. J. Alzheimer’s Dis. 20, 417–421 (2010). CAS Article Google Scholar Siebert, A. P. et al. Structural and functional similarities of calcium homeostasis modulator 1 (CALHM1) ion channel with connexins, pannexins, and innexins. J. Biol. Chem. 288, 6140–6153 (2013). CAS Article PubMed PubMed Central Google Scholar Tanis, J. E., Ma, Z. & Foskett, J. K. The NH2 terminus regulates voltage-dependent gating of CALHM ion channels. Am. J. Physiol. Cell Physiol. 313, C173–C186 (2017). Article PubMed PubMed Central Google Scholar Syrjanen, J. L. et al. Structure and assembly of calcium homeostasis modulator proteins. Nat. Struct. Mol. Biol. 27, 150–159 (2020). CAS Article PubMed PubMed Central Google Scholar Drozdzyk, K. et al. Cryo-EM structures and functional properties of CALHM channels of the human placenta. Elife 9, e55853 (2020). Choi, W. et al. The structures and gating mechanism of human calcium homeostasis modulator 2. Nature 576, 163–167 (2019). CAS Article PubMed Google Scholar Demura, K. et al. Cryo-EM structures of calcium homeostasis modulator channels in diverse oligomeric assemblies. Sci. Adv. 6, eaba8105 (2020). CAS Article PubMed PubMed Central Google Scholar Download references The authors acknowledge the cryo-EM facility and computing resources in Center of Cryo-Electron Microscopy, Shanghai Jiao Tong University. This work was supported by Ministry of Science and Technology (2020YFA090023 and 2016YFA0500404 to S.Y. and 2018YFA0508100 to J.G.), the National Natural Science Foundation of China (31525001 and 31971127 to S.Y., 31870724 to J.G., 31900041 to F.G. and 31525007 and 31930063 to M.L.), the Fundamental Research Funds for the Central Universities (to S.Y. and J.G.), and Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support (20181711 to J.W.). These authors contributed equally: Jie Liu, Futang Wan, Qiuheng Jin Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China Jie Liu, Qiuheng Jin, Eijaz Ahmed Bhat & Sheng Ye Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China Futang Wan, Ming Lei & Jian Wu Shanghai Institute of Precision Medicine, Shanghai 200125, China Futang Wan, Ming Lei & Jian Wu Department of Biophysics, Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China Xiaoxiao Li & Jiangtao Guo Department of Biophysics, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China Xiaoxiao Li & Jiangtao Guo State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China Ming Lei Key laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China Ming Lei Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, School of Life Sciences, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, China Fenghui Guan & Sheng Ye Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai 200125, China Jian Wu You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar J.L., Q.J., X.L., and E.A.B. purified the human CALHM5 channel. F.W. and J.L. prepared cryo-EM specimens, collected datasets and determined the structure. F.G. and J.W carried out model building and refinement. Q.J., F.G., M.L., and S.Y. wrote the manuscript. All authors contributed to data interpretation and the writing of the manuscript. S.Y. initiated the project, and S.Y. and J.W. orchestrated the project. Correspondence to Fenghui Guan or Jian Wu or Sheng Ye. The authors declare that they have no conflict...