Insights into the molecular mechanisms underlying mammalian P2X7 receptor functions and contributions in diseases, revealed by structural modeling and single nucleotide polymorphisms
- 1School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK
- 2INSERM U1069 Nutrition, Growth and Cancer, Université François-Rabelais de Tours, Tours, France
The mammalian P2X7 receptors (P2X7Rs), a member of the ionotropic P2X receptor family with distinctive functional properties, play an important part in mediating extracellular ATP signaling in health and disease. A clear delineation of the molecular mechanisms underlying the key receptor properties, such as ATP-binding, ion permeation, and large pore formation of the mammalian P2X7Rs, is still lacking, but such knowledge is crucial for a better understanding of their physiological functions and contributions in diseases and for development of therapeutics. The recent breakthroughs in determining the atomic structures of the zebrafish P2X4.1R in the closed and ATP-bound open states have provided the long-awaited structural information. The human P2RX7 gene is abundant with non-synonymous single nucleotide polymorphisms (NS-SNPs), which generate a repertoire of human P2X7Rs with point mutations. Characterizations of the NS-SNPs identified in patients of various disease conditions and the resulting mutations have informed previously unknown molecular mechanisms determining the mammalian P2X7R functions and diseases. In this review, we will discuss the new insights into such mechanisms provided by structural modeling and recent functional and genetic linkage studies of NS-SNPs.
Keywords: extracellular ATP, P2X7R, structural modeling, ATP-binding, ion channel, large pore, NS-SNPs
Citation: Jiang L-H, Baldwin JM, Roger S and Baldwin SA (2013) Insights into the molecular mechanisms underlying mammalian P2X7 receptor functions and contributions in diseases, revealed by structural modeling and single nucleotide polymorphisms. Front. Pharmacol. 4:55. doi: 10.3389/fphar.2013.00055
Received: 14 March 2013; Accepted: 11 April 2013;
Published online: 07 May 2013.
Edited by:Jean-François Desaphy, University of Bari “Aldo Moro,” Italy
Reviewed by:Elena Adinolfi, University of Ferrara, Italy
Mark T. Young, Cardiff University, UK
Orazio Nicolotti, University of Bari “Aldo Moro,” Italy
Copyright: © 2013 Jiang, Baldwin, Roger and Baldwin. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Lin-Hua Jiang, School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK. e-mail: firstname.lastname@example.org