Insights into the Molecular Mechanisms Underlying Mammalian P2X7 Receptor Functions and Contributions in Diseases, Revealed by Structural Modeling and Single Nucleotide Polymorphisms.
Insights into the Molecular Mechanisms Underlying Mammalian P2X7 Receptor Functions and Contributions in Diseases, Revealed by Structural Modeling and Single Nucleotide Polymorphisms.
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DOI：
10.3389/fphar.2013.00055
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发表时间：
2013
影响因子：
5.6
通讯作者：
Baldwin SA
中科院分区：
文献类型：
--
作者：
Jiang LH;Baldwin JM;Roger S;Baldwin SA
哺乳动物P2 X7受体（P2 X7 Rs）是亲离子型P2 X受体家族的成员，具有独特的功能特性，在健康和疾病中介导细胞外ATP信号转导中发挥重要作用。一个清晰的描绘的关键受体的特性，如ATP结合，离子渗透，和大孔形成的哺乳动物P2 X7 Rs的分子机制，仍然缺乏，但这样的知识是至关重要的，更好地了解他们的生理功能和疾病的贡献和治疗的发展。最近在确定斑马鱼P2X4.1R在封闭和ATP结合开放状态下的原子结构方面取得了突破，提供了期待已久的结构信息。人类P2 RX 7基因富含非同义单核苷酸多态性（NS-SNP），其产生具有点突变的人类P2 X7 R的库。在各种疾病状况的患者中鉴定的NS-SNP的表征和所产生的突变已经告知了先前未知的决定哺乳动物P2 X7 R功能和疾病的分子机制。在这篇综述中，我们将讨论新的见解，这种机制提供的结构建模和最近的功能和遗传连锁研究的NS-SNPs。
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.
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作者：
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DOI：
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发表时间：
2006-06-05
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