8bx7
Structure of the rod CNG channel bound to calmodulin
Structural highlights
FunctionCNGB1_BOVIN Pore-forming subunit of the rod cyclic nucleotide-gated channel. Mediates rod photoresponses at dim light converting transient changes in intracellular cGMP levels into electrical signals. In the dark, cGMP levels are high and keep the channel open enabling a steady inward current carried by Na(+) and Ca(2+) ions that leads to membrane depolarization and neurotransmitter release from synaptic terminals. Upon photon absorption cGMP levels decline leading to channel closure and membrane hyperpolarization that ultimately slows neurotransmitter release and signals the presence of light, the end point of the phototransduction cascade (PubMed:10352032, PubMed:21878911, PubMed:34969975, PubMed:37011209). Pore-forming subunit of the olfactory cyclic nucleotide-gated channel. Operates in the cilia of olfactory sensory neurons where chemical stimulation of the odorant is converted to an electrical signal. Mediates odorant-induced cAMP-dependent Ca(2+) influx triggering neuron depolarization. The rise of intracellular Ca(2+) levels potentiates the olfactory response by activating Ca(2+)-dependent Cl(-) channels, but it also serves as a negative feedback signal to desensitize the channel for rapid adaptation to odorants (By similarity). Conducts cGMP- and cAMP-gated ion currents, with permeability for monovalent and divalent cations. The selectivity for Ca(2+) over Na(+) increases with cGMP concentrations, whereas the selectivity among monovalent ions is independent of the cGMP levels (By similarity) (PubMed:10352032).[UniProtKB:A0A8I5ZN27][UniProtKB:Q9NQW8][1] [2] [3] [4] Publication Abstract from PubMedCalmodulin (CaM) regulates many ion channels to control calcium entry into cells, and mutations that alter this interaction are linked to fatal diseases. The structural basis of CaM regulation remains largely unexplored. In retinal photoreceptors, CaM binds to the CNGB subunit of cyclic nucleotide-gated (CNG) channels and, thereby, adjusts the channel's Cyclic guanosine monophosphate (cGMP) sensitivity in response to changes in ambient light conditions. Here, we provide the structural characterization for CaM regulation of a CNG channel by using a combination of single-particle cryo-electron microscopy and structural proteomics. CaM connects the CNGA and CNGB subunits, resulting in structural changes both in the cytosolic and transmembrane regions of the channel. Cross-linking and limited proteolysis-coupled mass spectrometry mapped the conformational changes induced by CaM in vitro and in the native membrane. We propose that CaM is a constitutive subunit of the rod channel to ensure high sensitivity in dim light. Our mass spectrometry-based approach is generally relevant for studying the effect of CaM on ion channels in tissues of medical interest, where only minute quantities are available. Structural basis of calmodulin modulation of the rod cyclic nucleotide-gated channel.,Barret DCA, Schuster D, Rodrigues MJ, Leitner A, Picotti P, Schertler GFX, Kaupp UB, Korkhov VM, Marino J Proc Natl Acad Sci U S A. 2023 Apr 11;120(15):e2300309120. doi: , 10.1073/pnas.2300309120. Epub 2023 Apr 3. PMID:37011209[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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