Direct Observation of ATP-Induced Conformational Changes in Single P2X_4 Receptors

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Direct Observation of ATP-Induced Conformational Changes in Single P2X_4 Receptors

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Article
Kyushu Univ. Production Kyushu Univ. Production
Responsibility:
Shinozaki, Youichi(NTT Basic Research Laboratories, NTT Corporation)
Sumitomo, Koji(NTT Basic Research Laboratories, NTT Corporation)
Tsuda, Makoto(Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University)

Koizumi, Schuichi(Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi)
Inoue, Kazuhide(Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University)
Torimitsu, Keiichi(NTT Basic Research Laboratories, NTT Corporation)
篠崎, 陽一(NTT物性科学基礎研究所)
住友, 弘二(NTT物性科学基礎研究所)
津田, 誠(九州大学大学院薬学研究院臨床薬学部門)
小泉, 修一(山梨大学大学院医学工学総合教育部薬理学教室)
井上, 和秀(九州大学大学院薬学研究院臨床薬学部門)
鳥光, 慶一(NTT物性科学基礎研究所)

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Language:
English
Publication info:
PLoS Biology. 7, (5), pp. e1000103-, 2009-05-05. Public Library of Science,PLoS
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Publisher
Abstract:
The ATP-gated P2X_4 receptor is a cation channel, which is important in various pathophysiological events. The architecture of the P2X_4 receptor in the activated state and how to change its structure in response to ATP binding are not fully understood. Here, we analyze the architecture and ATP-induced structural changes in P2X_4 receptors using fast-scanning atomic force microscopy (AFM). AFM images of the membrane-dissociated and membrane-inserted forms of P2X_4 receptors and a functional analysis revealed that P2X_4 receptors have an upward orientation on mica but lean to one side. Time-lapse imaging of the ATP-induced structural changes in P2X_4 receptors revealed two different forms of activated structures under 0 Ca^(2+) conditions, namely a trimer structure and a pore dilation-like tripartite structure. A dye uptake measurement demonstrated that ATP-activated P2X_4 receptors display pore dilation in the absence of Ca^(2+). With Ca^(2+), the P2X_4 receptors exhibited only a disengaged trimer and no dye uptake was observed. Thus our data provide a new insight into ATP-induced structural changes in P2X_4 receptors that correlate with pore dynamics. Read more
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