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TitleStructural mechanisms of gating and selectivity of human rod CNGA1 channel.
Journal, issue, pagesNeuron, Vol. 109, Issue 8, Page 1302-11313.e4, Year 2021
Publish dateApr 21, 2021
AuthorsJing Xue / Yan Han / Weizhong Zeng / Yan Wang / Youxing Jiang /
PubMed AbstractMammalian 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 ...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 Ca binding sites inside the selectivity filter, providing structural insights into Ca 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.
External linksNeuron / PubMed:33651975 / PubMed Central
MethodsEM (single particle)
Resolution2.6 - 3.6 Å
Structure data

EMDB-23306, PDB-7lft:
Cryo-EM structure of human Apo CNGA1 channel in K+/Ca2+
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-23307, PDB-7lfw:
Cryo-EM structure of human cGMP-bound open CNGA1 channel in K+/Ca2+
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-23308, PDB-7lfx:
Cryo-EM structure of human cGMP-bound open CNGA1 channel in Na+/Ca2+
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-23309, PDB-7lfy:
Cryo-EM structure of human cGMP-bound open CNGA1 channel in Na+
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-23310, PDB-7lg1:
Cryo-EM structure of human cGMP-bound CNGA1_E365Q channel in Na+/Ca2+
Method: EM (single particle) / Resolution: 2.7 Å

Chemicals

ChemComp-CLR:
CHOLESTEROL

ChemComp-CPL:
1-PALMITOYL-2-LINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / phospholipid*YM

ChemComp-K:
Unknown entry

ChemComp-HOH:
WATER

ChemComp-PCG:
CYCLIC GUANOSINE MONOPHOSPHATE

ChemComp-CA:
Unknown entry

ChemComp-NA:
Unknown entry

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / ALPHA-HELICAL / ION CHANNEL

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