Molecular determinants of permeation in a fluoride-specific ion channel

Fluoride ion channels of the Fluc family combat toxicity arising from accumulation of environmental F-. Although crystal structures are known, the densely packed pore region has precluded delineation of the ion pathway. Here we chart out the Fluc pore and characterize its chemical requirements for t...

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Main Authors: Nicholas B Last, Senmiao Sun, Minh C Pham, Christopher Miller
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2017-09-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/31259
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author Nicholas B Last
Senmiao Sun
Minh C Pham
Christopher Miller
author_facet Nicholas B Last
Senmiao Sun
Minh C Pham
Christopher Miller
author_sort Nicholas B Last
collection DOAJ
description Fluoride ion channels of the Fluc family combat toxicity arising from accumulation of environmental F-. Although crystal structures are known, the densely packed pore region has precluded delineation of the ion pathway. Here we chart out the Fluc pore and characterize its chemical requirements for transport. A ladder of H-bond donating residues creates a ‘polar track’ demarking the ion-conduction pathway. Surprisingly, while track polarity is well conserved, polarity is nonetheless functionally dispensable at several positions. A threonine at one end of the pore engages in vital interactions through its β-branched methyl group. Two critical central phenylalanines that directly coordinate F- through a quadrupolar-ion interaction cannot be functionally substituted by aromatic, non-polar, or polar sidechains. The only functional replacement is methionine, which coordinates F- through its partially positive γ-methylene in mimicry of phenylalanine’s quadrupolar interaction. These results demonstrate the unusual chemical requirements for selectively transporting the strongly H-bonding F- anion.
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spelling doaj.art-415a4dc8834c4cde87d1d475c80a797f2022-12-22T03:52:31ZengeLife Sciences Publications LtdeLife2050-084X2017-09-01610.7554/eLife.31259Molecular determinants of permeation in a fluoride-specific ion channelNicholas B Last0Senmiao Sun1Minh C Pham2Christopher Miller3https://orcid.org/0000-0002-0273-8653Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, United StatesDepartment of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, United StatesDepartment of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, United StatesDepartment of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, United StatesFluoride ion channels of the Fluc family combat toxicity arising from accumulation of environmental F-. Although crystal structures are known, the densely packed pore region has precluded delineation of the ion pathway. Here we chart out the Fluc pore and characterize its chemical requirements for transport. A ladder of H-bond donating residues creates a ‘polar track’ demarking the ion-conduction pathway. Surprisingly, while track polarity is well conserved, polarity is nonetheless functionally dispensable at several positions. A threonine at one end of the pore engages in vital interactions through its β-branched methyl group. Two critical central phenylalanines that directly coordinate F- through a quadrupolar-ion interaction cannot be functionally substituted by aromatic, non-polar, or polar sidechains. The only functional replacement is methionine, which coordinates F- through its partially positive γ-methylene in mimicry of phenylalanine’s quadrupolar interaction. These results demonstrate the unusual chemical requirements for selectively transporting the strongly H-bonding F- anion.https://elifesciences.org/articles/31259ion channelpermeationfluorideH-bond
spellingShingle Nicholas B Last
Senmiao Sun
Minh C Pham
Christopher Miller
Molecular determinants of permeation in a fluoride-specific ion channel
eLife
ion channel
permeation
fluoride
H-bond
title Molecular determinants of permeation in a fluoride-specific ion channel
title_full Molecular determinants of permeation in a fluoride-specific ion channel
title_fullStr Molecular determinants of permeation in a fluoride-specific ion channel
title_full_unstemmed Molecular determinants of permeation in a fluoride-specific ion channel
title_short Molecular determinants of permeation in a fluoride-specific ion channel
title_sort molecular determinants of permeation in a fluoride specific ion channel
topic ion channel
permeation
fluoride
H-bond
url https://elifesciences.org/articles/31259
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AT christophermiller moleculardeterminantsofpermeationinafluoridespecificionchannel