Caseley, EA orcid.org/0000-0001-7591-143X, Muench, SP orcid.org/0000-0001-6869-4414 and Jiang, L-H orcid.org/0000-0001-6398-0411 (2022) Tyrosine 288 in the extracellular domain of the human P2X7 receptor is critical for receptor function revealed by structural modeling and site-directed mutagenesis. Proteins: Structure, Function, and Bioinformatics, 90 (3). pp. 619-624. ISSN 0887-3585
Abstract
The P2X7 receptor (P2X7R) is a calcium-permeable cation channel activated by high concentrations of extracellular ATP. It plays a role in vital physiological processes, particularly in innate immunity, and is dysregulated in pathological conditions such as inflammatory diseases, neurodegenerative diseases, mood disorders, and cancers. Structural modeling of the human P2X7R (hP2X7R) based on the recently available structures of the rat P2X7 receptor (rP2XR) in conjunction with molecular docking predicts the orientation of tyrosine at position 288 (Y288) in the extracellular domain to face ATP. In this short communication, we combined site-directed mutagenesis and whole-cell patch-clamp recording to investigate the role of this residue in the hP2X7R function. Mutation of this extracellular residue to amino acids with different properties massively impaired current responses to both ATP and BzATP, suggesting that Y288 is important for normal receptor function. Such a finding facilitates development of an in-depth understanding of the molecular basis of hP2X7R structure–function relationships.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 Wiley Periodicals LLC. This is the peer reviewed version of the following article: Caseley, EA , Muench, SP and Jiang, L-H (2022) Tyrosine 288 in the extracellular domain of the human P2X7 receptor is critical for receptor function revealed by structural modeling and site-directed mutagenesis. Proteins: Structure, Function, and Bioinformatics, 90 (3). pp. 619-624. ISSN 0887-3585, which has been published in final form at [https://doi.org/10.1002/prot.26259]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | molecular docking, P2X7R, patch-clamp recording, site-directed mutagenesis, structural modeling, structure–function relationships |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Funding Information: | Funder Grant number Wellcome Trust 099758/Z/12/Z |
Depositing User: | Symplectic Publications |
Date Deposited: | 06 Oct 2021 12:09 |
Last Modified: | 08 Oct 2022 00:15 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/prot.26259 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:178808 |