Transient receptor potential (TRP) channels function as sensors for various physical and chemical stimuli and are vitally important players in regulation of key biochemical processes in a variety of cells. TRPV5 and TRPV6 subtypes of TRP channels are the main Ca2+ entry channels in epithelia Their pores are selective for Ca2+ and permeable for a variety of monovalent and divalent cations. An exact mechanism of Ca2+ permeation and selectivity through the TRPV5/6 ion channels is unknown. Recently, a crystal structure of the TRPV6 channel, the first high-resolution structure of a TRP channel, has been solved in complex with different ions bound in the channel pore [1]. Analysis of the structure suggested that Ca2+ permeates TRPV6 channel by a knock-off mechanism. We have created a fully atomistic model of the trans-membrane (TM) domain of the TRPV6 channel in lipid and water, and performed molecular dynamics simulations of Na+ , Ca2+, Ba2+ , and Gd3+ ion permeation through the selectivity filter of this channel. As a result, our MD simulations directly demonstrate the key features of ion permeation through TRPV6 channel pore. In particular, at low calcium concentrations, we observed interplay of Na+ and Ca2+ permeation that follows the knock-off mechanism. We also compare Ca2+ permeation with permeation of Ba 2+ and channel block by Gd3+.



Sakipov S, Sobolevsky AI, Kurnikova MG. Ion Permeation Mechanism in Epithelial Calcium Channel TRVP6 Sci Rep. 8(1):5715. (2018)



1. Saotome, Kei, Singh, A. K., Yelshanskaya, M. V., Sobolevsky, A. I. (2016) Crystal structure of the epithelial calcium channel TRPV6. Nature 534, 506-511


HEME transfer

Hb to NEAT domain HEME transfer

TRPV6 channel

Calcium Ion Channel

AMPA receptor dynamical allostery and gating mechanisms

Gating and mechanisms of channel activation and deactivation

NMDA receptor transmembrane domain structure and function

Mechanism of divalent ion selectivity - Mechanism of transmembrane domain (TMD) pore opening