TY - JOUR
T1 - Cryo-EM structures of apo and antagonist-bound human Cav3.1
AU - Zhao, Yanyu
AU - Huang, Gaoxingyu
AU - Wu, Qiurong
AU - Wu, Kun
AU - Li, Ruiqi
AU - Lei, Jianlin
AU - Pan, Xiaojing
AU - Yan, Nieng
N1 - Funding Information:
Acknowledgements We thank X. Li for technical support during EM image acquisition. We thank J. Han for sharing the cDNA for human Cav3.1 (Uniprot O43497-9). This work was funded by the National Natural Science Foundation of China (projects 81920108015, 31800628 and 31621092), and the National Key R&D Program (2016YFA0500402 to X.P. and 2016YFA0501100 to J.L.) from Ministry of Science and Technology of China. We thank the Tsinghua University Branch of China National Center for Protein Sciences (Beijing) for providing the cryo-EM facility support. We thank the computational facility support on the cluster of Bio-Computing Platform (Tsinghua University Branch of China National Center for Protein Sciences Beijing) and the ‘Explorer 100’ cluster system of Tsinghua National Laboratory for Information Science and Technology. N.Y. is supported by the Shirley M. Tilghman endowed professorship from Princeton University.
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2019/12/19
Y1 - 2019/12/19
N2 - Among the ten subtypes of mammalian voltage-gated calcium (Cav) channels, Cav3.1–Cav3.3 constitute the T-type, or the low-voltage-activated, subfamily, the abnormal activities of which are associated with epilepsy, psychiatric disorders and pain1–5. Here we report the cryo-electron microscopy structures of human Cav3.1 alone and in complex with a highly Cav3-selective blocker, Z9446,7, at resolutions of 3.3 Å and 3.1 Å, respectively. The arch-shaped Z944 molecule reclines in the central cavity of the pore domain, with the wide end inserting into the fenestration on the interface between repeats II and III, and the narrow end hanging above the intracellular gate like a plug. The structures provide the framework for comparative investigation of the distinct channel properties of different Cav subfamilies.
AB - Among the ten subtypes of mammalian voltage-gated calcium (Cav) channels, Cav3.1–Cav3.3 constitute the T-type, or the low-voltage-activated, subfamily, the abnormal activities of which are associated with epilepsy, psychiatric disorders and pain1–5. Here we report the cryo-electron microscopy structures of human Cav3.1 alone and in complex with a highly Cav3-selective blocker, Z9446,7, at resolutions of 3.3 Å and 3.1 Å, respectively. The arch-shaped Z944 molecule reclines in the central cavity of the pore domain, with the wide end inserting into the fenestration on the interface between repeats II and III, and the narrow end hanging above the intracellular gate like a plug. The structures provide the framework for comparative investigation of the distinct channel properties of different Cav subfamilies.
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U2 - 10.1038/s41586-019-1801-3
DO - 10.1038/s41586-019-1801-3
M3 - Article
C2 - 31766050
AN - SCOPUS:85076599200
SN - 0028-0836
VL - 576
SP - 492
EP - 497
JO - Nature
JF - Nature
IS - 7787
ER -