8EPM
Human R-type voltage-gated calcium channel Cav2.3 CH2II-deleted mutant at 3.1 Angstrom resolution
Summary for 8EPM
| Entry DOI | 10.2210/pdb8epm/pdb |
| EMDB information | 28530 |
| Descriptor | Voltage-dependent R-type calcium channel subunit alpha-1E, Voltage-dependent calcium channel subunit alpha-2/delta-1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | cav2.3, channels, calcium ion-selective, transport protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 390020.62 |
| Authors | |
| Primary citation | Yao, X.,Wang, Y.,Wang, Z.,Fan, X.,Wu, D.,Huang, J.,Mueller, A.,Gao, S.,Hu, M.,Robinson, C.V.,Yu, Y.,Gao, S.,Yan, N. Structures of the R-type human Ca v 2.3 channel reveal conformational crosstalk of the intracellular segments. Nat Commun, 13:7358-7358, 2022 Cited by PubMed Abstract: The R-type voltage-gated Ca (Ca) channels Ca2.3, widely expressed in neuronal and neuroendocrine cells, represent potential drug targets for pain, seizures, epilepsy, and Parkinson's disease. Despite their physiological importance, there have lacked selective small-molecule inhibitors targeting these channels. High-resolution structures may aid rational drug design. Here, we report the cryo-EM structure of human Ca2.3 in complex with α2δ-1 and β3 subunits at an overall resolution of 3.1 Å. The structure is nearly identical to that of Ca2.2, with VSD in the down state and the other three VSDs up. A phosphatidylinositol 4,5-bisphosphate (PIP2) molecule binds to the interface of VSD and the tightly closed pore domain. We also determined the cryo-EM structure of a Ca2.3 mutant in which a Ca2-unique cytosolic helix in repeat II (designated the CH2 helix) is deleted. This mutant, named ΔCH2, still reserves a down VSD, but PIP2 is invisible and the juxtamembrane region on the cytosolic side is barely discernible. Our structural and electrophysiological characterizations of the wild type and ΔCH2 Ca2.3 show that the CH2 helix stabilizes the inactivated conformation of the channel by tightening the cytosolic juxtamembrane segments, while CH2 helix is not necessary for locking the down state of VSD. PubMed: 36446785DOI: 10.1038/s41467-022-35026-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
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