Structural modeling of selectivity filter in transient receptor pontential melastatin 8 ion channel

Abstract

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.