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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.


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


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.


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 wordsTransient receptor potential channels      TRPM cation channels      Amino acid sequence      Computer simulation     
Received: 25 July 2018      Published: 10 May 2019
CLC:  Q71  
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.

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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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