Work

Structural mechanisms of assembly, gating, and calmodulin modulation of human olfactory CNG channel

Year: 2025

Type: article

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 2+ /CaM-mediated rapid inhibition of the native olfactory CNG channel.

Source: Nature Communications

DOI: 10.1038/s41467-025-64436-5

Authors: Jing Xue, Ninghai Gan, Weizhong Zeng, Youxing Jiang

Institutions: Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center

Language: English

Topic: Ion channel regulation and function

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $6,990