7VFS

Human N-type voltage gated calcium channel CaV2.2-alpha2/delta1-beta1 complex, apo state

Summary for 7VFS

• Entry DOI: 10.2210/pdb7vfs/pdb
• EMDB information: 31958
• Descriptor: Voltage-dependent N-type calcium channel subunit alpha-1B, 2-acetamido-2-deoxy-beta-D-glucopyranose, Voltage-dependent calcium channel subunit alpha-2/delta-1, ... (10 entities in total)
• Functional Keywords: voltage gated calcium channel, n-type, complex, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 463516.49

Authors

Dong, Y.,Gao, Y.,Wang, Y.,Zhao, Y. (deposition date: 2021-09-13, release date: 2021-11-03, Last modification date: 2024-10-09)

Primary citation

Dong, Y.,Gao, Y.,Xu, S.,Wang, Y.,Yu, Z.,Li, Y.,Li, B.,Yuan, T.,Yang, B.,Zhang, X.C.,Jiang, D.,Huang, Z.,Zhao, Y.
Closed-state inactivation and pore-blocker modulation mechanisms of human Ca V 2.2.
Cell Rep, 37:109931-109931, 2021

PubMed Abstract: N-type voltage-gated calcium (Ca) channels mediate Ca influx at presynaptic terminals in response to action potentials and play vital roles in synaptogenesis, release of neurotransmitters, and nociceptive transmission. Here, we elucidate a cryo-electron microscopy (cryo-EM) structure of the human Ca2.2 complex in apo, ziconotide-bound, and two Ca2.2-specific pore blockers-bound states. The second voltage-sensing domain (VSD) is captured in a resting-state conformation, trapped by a phosphatidylinositol 4,5-bisphosphate (PIP) molecule, which is distinct from the other three VSDs of Ca2.2, as well as activated VSDs observed in previous structures of Ca channels. This structure reveals the molecular basis for the unique inactivation process of Ca2.2 channels, in which the intracellular gate formed by S6 helices is closed and a W-helix from the domain II-III linker stabilizes closed-state inactivation. The structures of this inactivated, drug-bound complex lay a solid foundation for developing new state-dependent blockers for treatment of chronic pain.

PubMed: 34731621
DOI: 10.1016/j.celrep.2021.109931

Experimental method

ELECTRON MICROSCOPY (2.8 Å)