A CLC-type F−/H+ antiporter in ion-swapped conformations

Details

• Alternative Title:
  Nat Struct Mol Biol
• Personal Author:
  Last, Nicholas B. ; Stockbridge, Randy B. ; Lajoie, Ashley E. ; Shane, Tania ; Kolmakova-Partensky, Ludmila ; Koide, Akiko ; Koide, Shohei ; Miller, Christopher
• Description:
  Fluoride/proton antiporters of the CLC| family combat F| toxicity in bacteria by exporting this halide from the cytoplasm. These transporters belong to the widespread CLC superfamily but display transport properties different from those of the well-studied Cl|/H| antiporters. Here, we report a structural and functional investigation of these F|-transport proteins. Crystal structures of a CLC| homolog from Enterococcus casseliflavus are captured in two conformations with simultaneous accessibility of F| and H| ions via separate pathways on opposite sides of the membrane. Manipulation of a key glutamate residue critical for H| and F| transport reverses the anion selectivity of transport; replacement of the glutamate with glutamine or alanine completely inhibits F| and H| transport while allowing for rapid uncoupled flux of Cl|. The structural and functional results lead to a 'windmill' model of CLC antiport wherein F| and H| simultaneously move through separate ion-specific pathways that switch sidedness during the transport cycle.
• Subjects:
  Article
• Source:
  Nat Struct Mol Biol. 25(7):601-606
• Pubmed ID:
  29941917
• Pubmed Central ID:
  PMC6044475
• Document Type:
  Journal Article
• Funding:
  Howard Hughes Medical Institute/United States ; R01 GM107023/NIGMS NIH HHS/National Institute of General Medical Sciences/United States ; S10 OD021832/ODCDC CDC HHS/Office of the Director/United States ; T32 GM007596/NIGMS NIH HHS/National Institute of General Medical Sciences/United States
• Volume:
  25
• Issue:
  7
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:1375ccf5c2309155d471885872cac47b7b369b4fd733478fdd19651c7aae4b2a
• Download URL:
  https://stacks.cdc.gov/view/cdc/80353/cdc_80353_DS1.pdf
• File Type:
  [PDF - 1.09 MB ]