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浙江大学学报（医学版）
J Zhejiang Univ (Med Sci)  2019, Vol. 48 Issue (1): 19-24    DOI: 10.3785/j.issn.1008-9292.2019.02.04
    
Structural modeling of selectivity filter in transient receptor pontential melastatin 8 ion channel
XU Lizhen(),YANG Fan
Department of Biophysics, Zhejiang University School of Medicine, Hangzhou 310058, China
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Abstract   Objective

To construct a three-dimensional structural model for the selectivity filter in the transient receptor pontential melastatin 8 (TRPM8) ion channel.

 Methods

In the Rosetta computational structural biology suite, multiple rounds of de novo modeling with the kinematic loop closure algorithm were performed.

 Results

After nine rounds of computational modeling, we obtained the models of the selectivity filter within the TRPM8 channel with the lowest energy and high convergence. The model showed that the sidechain of D918 points were away from the central ion permeation pathway, while the sidechains of Q914, D920 and T923 pointed towards it.The glycosylation site N934 was located outside the pore region and its side chain directed to the extracellular water environment.

 Conclusion

A three-dimensional structural model for the selectivity filter in the TRPM8 ion channel was constructed, which provides reliable structural information for exploring the mechanism of ion selectivity.

Key words： Transient receptor potential channels      TRPM cation channels      Amino acid sequence      Computer simulation     
Received: 25 July 2018      Published: 10 May 2019
CLC:  Q71  
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XU Lizhen
YANG Fan
Cite this article:

XU Lizhen,YANG Fan. Structural modeling of selectivity filter in transient receptor pontential melastatin 8 ion channel. J Zhejiang Univ (Med Sci), 2019, 48(1): 19-24.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2019.02.04     OR     http://www.zjujournals.com/med/Y2019/V48/I1/19


瞬时受体电位M8型离子通道选择性滤器的三维结构计算建模

目的

构建瞬时受体电位M8型（TRPM8）离子通道选择性滤器结构域的三维结构模型。

 方法

在Rosetta计算结构生物学工具包中，使用基于运动回路闭合算法的从头计算，对TRPM8离子通道选择性滤器结构域进行多轮计算建模。

 结果

经过9轮计算得到了能量最低且结构收敛的TRPM8通道选择性滤器结构域的三维结构模型，发现D918位点的侧链并不指向离子流过的孔区中心，而Q914、D920和T923位点的侧链指向孔区中心；糖基化位点N934位于孔区外侧，其侧链指向胞外水环境。

 结论

构建了TRPM8通道选择性滤器结构域的三维结构模型，为理解该通道的离子选择性及相关机制提供了较为可靠的结构信息。

关键词： 瞬时受体电位通道,  TRPM阳离子通道,  氨基酸序列,  计算机模拟 
Figure 1 The cryo-electron microscopy structure model of the transient receptor pontential melastatin 8 (TRPM8) channel and its corresponding electron density map
Figure 2 Amino acids sequence alignment of TRPM8FA (ficedula albicollis) and TRPM8model (mouse)
Figure 3 Energy-root mean square error plots of our models and the top 5 models with the lowest energy after 9 rounds of KIC modeling
Figure 4 Our model and the electron density map from the cryo-electron microscopy study
Figure 5 Residues point toward (green) and away (red) from the central ion permeation pathway mapped on our model
Figure 6 The residue N934 involved in glycosylation mapped on our model
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