Creator |
|
|
|
|
|
|
Language |
|
Publisher |
|
|
Date |
|
Source Title |
|
Vol |
|
Issue |
|
First Page |
|
Publication Type |
|
Access Rights |
|
Rights |
|
Related DOI |
|
Related DOI |
|
|
Related URI |
|
|
Related URI |
|
Related HDL |
|
Relation |
|
|
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.show more
|