8EVA

Cryo-EM structure of cGMP bound truncated human CNGA3/CNGB3 channel in lipid nanodisc, transition state 2

8EVA の概要

• エントリーDOI: 10.2210/pdb8eva/pdb
• EMDBエントリー: 28595 28603 28611 28620 28621 28624
• 分子名称: Cyclic nucleotide-gated cation channel alpha-3, Cyclic nucleotide-gated cation channel beta-3, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: cnga3, cngb3, ligand-bound, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 276890.11

構造登録者

Hu, Z.,Yang, J. (登録日: 2022-10-20, 公開日: 2023-08-09, 最終更新日: 2024-10-23)

主引用文献

Hu, Z.,Zheng, X.,Yang, J.
Conformational trajectory of allosteric gating of the human cone photoreceptor cyclic nucleotide-gated channel.
Nat Commun, 14:4284-4284, 2023

PubMed Abstract: Cyclic nucleotide-gated (CNG) channels transduce chemical signals into electrical signals in sensory receptors and neurons. They are activated by cGMP or cAMP, which bind to the cyclic nucleotide-binding domain (CNBD) to open a gate located 50-60 Å away in the central cavity. Structures of closed and open vertebrate CNG channels have been solved, but the conformational landscape of this allosteric gating remains to be elucidated and enriched. Here, we report structures of the cGMP-activated human cone photoreceptor CNGA3/CNGB3 channel in closed, intermediate, pre-open and open states in detergent or lipid nanodisc, all with fully bound cGMP. The pre-open and open states are obtained only in the lipid nanodisc, suggesting a critical role of lipids in tuning the energetic landscape of CNGA3/CNGB3 activation. The different states exhibit subunit-unique, incremental and distinct conformational rearrangements that originate in the CNBD, propagate through the gating ring to the transmembrane domain, and gradually open the S6 cavity gate. Our work illustrates a spatial conformational-change wave of allosteric gating of a vertebrate CNG channel by its natural ligand and provides an expanded framework for studying CNG properties and channelopathy.

PubMed: 37463923
DOI: 10.1038/s41467-023-39971-8

実験手法

ELECTRON MICROSCOPY (3.33 Å)