Structural mechanisms of gating and selectivity of human rod CNGA1 channel

Jing Xue, Yan Han, Weizhong Zeng, Yan Wang, Youxing Jiang

Research output: Contribution to journalArticlepeer-review

Abstract

Mammalian cyclic nucleotide-gated (CNG) channels play an essential role in the signal transduction of the visual and olfactory sensory systems. Here we reveal the structural mechanism of ligand gating in human rod CNGA1 channel by determining its cryo-EM structures in both the apo closed and cGMP-bound open states. Distinct from most other members of voltage-gated tetrameric cation channels, CNGA1 forms a central channel gate in the middle of the membrane, occluding the central cavity. Structural analyses of ion binding profiles in the selectivity filters of the wild-type channel and the E365Q filter mutant allow us to unambiguously define the two Ca2+ binding sites inside the selectivity filter, providing structural insights into Ca2+ blockage and permeation in CNG channels. The structure of the E365Q mutant also reveals two alternative side-chain conformations at Q365, providing a plausible explanation for the voltage-dependent gating of CNG channel acquired upon E365 mutation.

Original languageEnglish (US)
Pages (from-to)1302-1313.e4
JournalNeuron
Volume109
Issue number8
DOIs
StatePublished - Apr 21 2021

Keywords

  • CNG channel
  • Ca blockage and permeation
  • cGMP activation
  • cyclic nucleotide-gated
  • signal transduction
  • visual and olfactory sensory system

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Structural mechanisms of gating and selectivity of human rod CNGA1 channel'. Together they form a unique fingerprint.

Cite this