Title: Molecular determinants of permeation through the cation channel TRPM6
Authors: Topala, Catalin N ×
Groenestege, Wouter Tiel
Thébault, Stéphanie
van den Berg, Dennis
Nilius, Bernd
Hoenderop, Joost G
Bindels, René J #
Issue Date: Jun-2007
Publisher: Elsevier
Series Title: Cell Calcium vol:41 issue:6 pages:513-523
Abstract: TRPM6 and its closest relative TRPM7 are members of the Transient Receptor Potential Melastatin (TRPM) subfamily of cation channels and are known to be Mg(2+) permeable. By aligning the sequence of the putative TRPM6 pore with the pore sequences of the other subfamily members, we located in the loop between the fifth and the sixth transmembrane domain, a stretch of amino acids residues, (1028)GEIDVC(1033), as the potential selectivity filter. Two negatively charged residues, E(1024) (conserved in TRPM6, TRPM7, TRPM1 and TRPM3) and D(1031) (conserved along the entire TRPM subfamily), were identified as important determinants of cation permeation through TRPM6, because neutralization of both residues into an alanine resulted in non-functional channels. Neutralization of E(1029) (conserved in TRPM6, TRPM7, TRPM4 and TRPM5) resulted in channels with increased conductance for Ba(2+) and Zn(2+), decreased ruthenium red sensitivity and larger pore diameter compared to wild-type TRPM6. Changing the residue I(1030) into methionine, resulted in channels with lower conductance for Ni(2+), decreased sensitivity to ruthenium red block and reduced pore diameter. Thus, these data demonstrate that amino acid residues E(1024), I(1030) and D(1031) are important for channel function and that subtle amino acid variation in the pore region accounts for TRPM6 permeation properties.
ISSN: 0143-4160
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Ion Channel Research
Department of Cellular and Molecular Medicine - miscellaneous
× corresponding author
# (joint) last author

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