9UPG

Cryo-EM structure of human olfactory CNGA2/A4/B1 in CaM-bound closed state

Summary for 9UPG

• Entry DOI: 10.2210/pdb9upg/pdb
• EMDB information: 64395
• Descriptor: Cyclic nucleotide-gated channel alpha-2, Cyclic nucleotide-gated channel alpha-4, Cyclic nucleotide-gated channel beta-1, ... (5 entities in total)
• Functional Keywords: ion channel, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 375282.61

Authors

Xue, J.,Jiang, Y. (deposition date: 2025-04-28, release date: 2025-09-24, Last modification date: 2026-04-08)

Primary citation

Xue, J.,Gan, N.,Zeng, W.,Jiang, Y.
Structural mechanisms of assembly, gating, and calmodulin modulation of human olfactory CNG channel.
Nat Commun, 16:9380-9380, 2025

PubMed Abstract: Mammalian cyclic nucleotide-gated (CNG) channels play crucial roles in visual and olfactory signal transduction. In olfactory sensory neurons, the native CNG channel functions as a heterotetramer consisting of CNGA2, CNGA4, and CNGB1b subunits and is activated by cAMP. Calmodulin (CaM) modulates the activity of the olfactory CNG channel, enabling rapid adaptation to odorants. Here we present cryo-EM structures of the native human olfactory CNGA2/A4/B1b channel in both CaM-bound closed and cAMP-bound open states, elucidating the molecular basis of the 2:1:1 subunit stoichiometry in channel assembly and the asymmetrical channel gating upon cAMP activation. Combining structural and functional analyses with AlphaFold prediction, we define two distinct CaM binding sites (CaM1 and CaM2) on the N- and C-terminal regions of CNGB1b, respectively, shedding light on the molecular mechanism of Ca/CaM-mediated rapid inhibition of the native olfactory CNG channel.

PubMed: 41131016
DOI: 10.1038/s41467-025-64436-5

Experimental method

ELECTRON MICROSCOPY (2.87 Å)