7rhh | pdb_00007rhh
Cryo-EM structure of human rod CNGA1/B1 channel in cGMP-bound openI state
Structural highlights
DiseaseCNGA1_HUMAN Retinitis pigmentosa. The disease is caused by variants affecting the gene represented in this entry. FunctionCNGA1_HUMAN Subunit of the rod cyclic GMP-gated cation channel, which is involved in the final stage of the phototransduction pathway. When light hits rod photoreceptors, cGMP concentrations decrease causing rapid closure of CNGA1/CNGB1 channels and, therefore, hyperpolarization of the membrane potential.[UniProtKB:Q00194] Publication Abstract from PubMedMammalian cyclic nucleotide-gated (CNG) channels are nonselective cation channels activated by cGMP or cAMP and play essential roles in the signal transduction of the visual and olfactory sensory systems. CNGA1, the principal component of the CNG channel from rod photoreceptors, can by itself form a functional homotetrameric channel and has been used as the model system in the majority of rod CNG studies. However, the native rod CNG functions as a heterotetramer consisting of three A1 and one B1 subunits and exhibits different functional properties than the CNGA1 homomer. Here we present the functional analysis of human rod CNGA1/B1 heterotetramer and its cryo-EM structures in apo, cGMP-bound, cAMP-bound, and L-cis-Diltiazem-blocked states. These structures, with resolution ranging from 2.6 to 3.3 A, elucidate the structural mechanisms underlying the 3:1 subunit stoichiometry, the asymmetrical gating upon cGMP activation, and the unique pharmacological property of the native rod CNG channel. Structural mechanisms of assembly, permeation, gating, and pharmacology of native human rod CNG channel.,Xue J, Han Y, Zeng W, Jiang Y Neuron. 2022 Jan 5;110(1):86-95.e5. doi: 10.1016/j.neuron.2021.10.006. Epub 2021 , Oct 25. PMID:34699778[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
