P2X受体运行和多聚化的关键点：对诱变研究基础结构的概述

Title:Key Sites for P2X Receptor Function and Multimerization: Overview of Mutagenesis Studies on a Structural Basis

Volume: 22 Issue: 7

Author(s): Ralf Hausmann, Achim Kless and Gunther Schmalzing

Affiliation:

关键词: 突变P2X受体分析， P2X组装领域， P2X ATP结合口袋， P2X四级结构， P2X受体功能。

摘要: P2X receptors constitute a seven-member family (P2X1-7) of extracellular ATP-gated cation channels of widespread expression. Because P2X receptors have been implicated in neurological, inflammatory and cardiovascular diseases, they constitute promising drug targets. Since the first P2X cDNA sequences became available in 1994, numerous site-directed mutagenesis studies have been conducted to disclose key sites of P2X receptor function and oligomerization. The publication of the 3-A crystal structures of the zebrafish P2X4 (zfP2X4) receptor in the homotrimeric apo-closed and ATP-bound open states in 2009 and 2012, respectively, has ushered a new era by allowing for the interpretation of the wealth of molecular data in terms of specific three-dimensional models and by paving the way for designing more-decisive experiments. Thanks to these structures, the last five years have provided invaluable insight into our understanding of the structure and function of the P2X receptor class of ligandgated ion channels. In this review, we provide an overview of mutagenesis studies of the pre- and post-crystal structure eras that identified amino acid residues of key importance for ligand binding, channel gating, ion flow, formation of the pore and the channel gate, and desensitization. In addition, the sites that are involved in the trimerization of P2X receptors are reviewed based on mutagenesis studies and interface contacts that were predicted by the zfP2X4 crystal structures.

Cite this article as:

Ralf Hausmann, Achim Kless and Gunther Schmalzing , Key Sites for P2X Receptor Function and Multimerization: Overview of Mutagenesis Studies on a Structural Basis, Current Medicinal Chemistry 2015; 22 (7) . https://dx.doi.org/10.2174/0929867322666141128163215