Structure versus function: Are new conformations of pannexin 1 yet to be resolved?
Structure versus function: Are new conformations of pannexin 1 yet to be resolved?
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DOI：
10.1085/jgp.202012754
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发表时间：
2021-05-03
期刊：
影响因子：
--
通讯作者：
Dahl G
中科院分区：
文献类型：
--
作者：
Mim C;Perkins G;Dahl G
Mim等人讨论了泛连接蛋白1作为ATP和氯离子通道的已知功能与最近发表的cryo-EM结构数据之间的差异，到目前为止，这些数据似乎仅与氯离子通道功能一致。Pannexin 1（Panx 1）在多种生理和病理环境中起决定性作用，包括向组织输送氧气、气道中的粘膜纤毛清除、脓毒症、神经性疼痛和癫痫。普遍认为Panx 1通过提供ATP的跨膜途径在嘌呤能信号传导中发挥作用。然而，在某些条件下，Panx 1也可以作为一个高度选择性的氯离子膜通道，而没有ATP的渗透性。最近的一系列出版物提供了有关Panx 1通道的结构信息。然而，虽然这些结构与氯离子选择性通道一致，但没有一个显示出对Panx 1的ATP释放功能具有强有力支持的构象。在这个观点中，我们批判性地评估了Panx 1通道的功能和结构的现有证据，并得出结论，ATP渗透途径对应的结构尚未确定。我们还列出了一组需要注意的其他主题，并提出了实现Panx 1通道的大孔，ATP可渗透构象的方法。
Mim et al. discuss discrepancies between the known functions of pannexin 1 as an ATP and chloride channel and recently published cryo-EM structural data, which so far appear consistent only with the chloride channel function. Pannexin 1 (Panx1) plays a decisive role in multiple physiological and pathological settings, including oxygen delivery to tissues, mucociliary clearance in airways, sepsis, neuropathic pain, and epilepsy. It is widely accepted that Panx1 exerts its role in the context of purinergic signaling by providing a transmembrane pathway for ATP. However, under certain conditions, Panx1 can also act as a highly selective membrane channel for chloride ions without ATP permeability. A recent flurry of publications has provided structural information about the Panx1 channel. However, while these structures are consistent with a chloride selective channel, none show a conformation with strong support for the ATP release function of Panx1. In this Viewpoint, we critically assess the existing evidence for the function and structure of the Panx1 channel and conclude that the structure corresponding to the ATP permeation pathway is yet to be determined. We also list a set of additional topics needing attention and propose ways to attain the large-pore, ATP-permeable conformation of the Panx1 channel.
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影响因子：
12.4
作者：
de Vasconcelos NM;Van Opdenbosch N;Van Gorp H;Parthoens E;Lamkanfi M
通讯作者：
Lamkanfi M
影响因子：
4.6
作者：
Epp, Anna L.;Ebert, Sarah N.;Swayne, Leigh Anne
通讯作者：
Swayne, Leigh Anne
影响因子：
5.4
作者：
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通讯作者：
Dermietzel, Rolf
影响因子：
8.3
作者：
Gido, G;Kristian, T;Siesjo, BK
通讯作者：
Siesjo, BK
DOI：
10.1073/pnas.2233464100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Bruzzone, R;Hormuzdi, SG;Monyer, H
通讯作者：
Monyer, H