Nucleotidegated

Nucleotidegated is a term used to describe proteins whose activity is regulated by the binding of a nucleotide. In the context of ion channels, nucleotidegated channels open in response to nucleotide binding, most commonly to ATP or cyclic nucleotides such as cAMP or cGMP. The term also appears in broader contexts to describe enzymes or transporters whose activity is modulated by nucleotide binding, though it is most common in channel pharmacology.

The mechanism involves a nucleotide-binding domain that undergoes a conformational change when a nucleotide binds. For example, P2X receptors are trimeric ligand-gated ion channels that open upon extracellular ATP binding, allowing cations to pass. Cyclic nucleotide-gated (CNG) channels possess a cytoplasmic cyclic nucleotide-binding domain; binding of cAMP or cGMP gates the pore, contributing to sensory transduction in rod and cone cells and olfactory neurons. In some cases, nucleotide binding modulates gating allosterically rather than triggering opening by itself.

Physiological roles include rapid signal transduction in nervous tissue, phototransduction in the retina, and sensory processing. Dysregulation of nucleotidegated channels has been implicated in various diseases and disorders, ranging from neuropathies to retinal dysfunctions and pain signaling. Pharmacological agents targeting nucleotidegated channels are used in research and, in some instances, therapeutically.

Classification and terminology: although "nucleotidegated" is used informally, the main established families are ATP-gated P2X receptors and cyclic-nucleotide-gated (CNG) channels. The concept overlaps with other nucleotide-binding proteins, including GTPases and ATPases, but those are typically not described as "nucleotidegated" channels.