The permeation mechanism of organic cations through a CNG mimic channel

CORC > 宁波材料技术与工程研究所 > 中国科学院宁波材料技术与工程研究所 > 2018专题

	The permeation mechanism of organic cations through a CNG mimic channel
	Marchesi, Arin; Rodriguez, Alex; De March, Matteo; Onesti, Silvia; Laio, Alessandro; Torre, Vincent; Napolitano, Luisa M. R.
刊名	PLOS COMPUTATIONAL BIOLOGY
	2018
卷号	14 期号:8
关键词	Nucleotide-gated Channels Potassium Channels Ion Selectivity Calcium Channels K++ Channel Pore Conduction Binding Rods Permeability
英文摘要	Several channels, ranging from TRP receptors to Gap junctions, allow the exchange of small organic solute across cell membrane. However, very little is known about the molecular mechanism of their permeation. Cyclic Nucleotide Gated (CNG) channels, despite their homology with K+ channels and in contrast with them, allow the passage of larger methylated and ethylated ammonium ions like dimethylammonium (DMA) and ethylammonium (EA). We combined electrophysiology and molecular dynamics simulations to examine how DMA interacts with the pore and permeates through it. Due to the presence of hydrophobic groups, DMA enters easily in the channel and, unlike the alkali cations, does not need to cross any barrier. We also show that while the crystal structure is consistent with the presence of a single DMA ion at full occupancy, the channel is able to conduct a sizable current of DMA ions only when two ions are present inside the channel. Moreover, the second DMA ion dramatically changes the free energy landscape, destabilizing the crystallographic binding site and lowering by almost 25 kJ/mol the binding affinity between DMA and the channel. Based on the results of the simulation the experimental electron density maps can be reinterpreted with the presence of a second ion at lower occupancy. In this mechanism the flexibility of the channel plays a key role, extending the classical multi-ion permeation paradigm in which conductance is enhanced by the plain interaction between the ions.
学科主题	Science & Technology - Other Topics ; Materials Science
语种	英语
公开日期	2018-12-04
内容类型	期刊论文
源URL	[http://ir.nimte.ac.cn/handle/174433/17272]
专题	2018专题
推荐引用方式 GB/T 7714	Marchesi, Arin,Rodriguez, Alex,De March, Matteo,et al. The permeation mechanism of organic cations through a CNG mimic channel[J]. PLOS COMPUTATIONAL BIOLOGY,2018,14(8).
APA	Marchesi, Arin.,Rodriguez, Alex.,De March, Matteo.,Onesti, Silvia.,Laio, Alessandro.,...&Napolitano, Luisa M. R..(2018).The permeation mechanism of organic cations through a CNG mimic channel.PLOS COMPUTATIONAL BIOLOGY,14(8).
MLA	Marchesi, Arin,et al."The permeation mechanism of organic cations through a CNG mimic channel".PLOS COMPUTATIONAL BIOLOGY 14.8(2018).