Structural insights into the nucleotide base specificity of P2X receptors
| Autor: | Go Kasuya, Kazushige Touhara, Yuichiro Fujiwara, Osamu Nureki, Yuji Furutani, Motoyuki Hattori, Satoshi Ryu, Ryuichiro Ishitani, Hisao Tsukamoto, Satoshi Morinaga |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Agonist medicine.drug_class Stereochemistry Cytidine Triphosphate Article Xenopus laevis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Side chain medicine Animals heterocyclic compounds Nucleotide Binding site Receptor Zebrafish chemistry.chemical_classification Binding Sites Multidisciplinary Hydrogen bond Zebrafish Proteins Molecular Docking Simulation 030104 developmental biology Membrane protein chemistry Biochemistry Receptors Purinergic P2X 030217 neurology & neurosurgery Cytosine Protein Binding |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep45208 |
| Popis: | P2X receptors are trimeric ATP-gated cation channels involved in diverse physiological processes, ranging from muscle contraction to nociception. Despite the recent structure determination of the ATP-bound P2X receptors, the molecular mechanism of the nucleotide base specificity has remained elusive. Here, we present the crystal structure of zebrafish P2X4 in complex with a weak affinity agonist, CTP, together with structure-based electrophysiological and spectroscopic analyses. The CTP-bound structure revealed a hydrogen bond, between the cytosine base and the side chain of the basic residue in the agonist binding site, which mediates the weak but significant affinity for CTP. The cytosine base is further recognized by two main chain atoms, as in the ATP-bound structure, but their bond lengths seem to be extended in the CTP-bound structure, also possibly contributing to the weaker affinity for CTP over ATP. This work provides the structural insights for the nucleotide base specificity of P2X receptors. |
| Databáze: | OpenAIRE |
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