Journal
SCIENTIFIC REPORTS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep45208
Keywords
-
Categories
Funding
- National Natural Science Foundation of China [31650110469, 31570838]
- Ministry of Science and Technology of China [2016YFA0502800]
- Platform for Drug Discovery, Informatics and Structural Life Science from MEXT
- JSPS KAKENHI [22117007, 25291011, 26708002, 24227004]
- FIRST program
- PRESTO, JST
- Office of Global Experts Recruitment in China
- ERATO Touhara Chemosensory Signal Project from JST, Japan
- CREST program
- Grants-in-Aid for Scientific Research [26708002, 22117007, 26640047, 17H03640] Funding Source: KAKEN
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available