A mechanism of regulating transmembrane potassium flux through a ligand-mediated conformational switch

T. P. Roosild, Samantha Miller, Ian Rylance Booth, S. Choe

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

The regulation of cation content is critical for cell growth. However, the molecular mechanisms that gate the systems that control K+ movements remain unclear. KTN is a highly conserved cytoplasmic domain present ubiquitously in a variety of prokaryotic and eukaryotic K+ channels and transporters. Here we report crystal structures for two representative KTN domains that reveal a dimeric hinged assembly. Alternative ligands NAD(+) and NADH block or vacate, respectively, the hinge region affecting the dimer's conformational flexibility. Conserved, surface-exposed hydrophobic patches that become coplanar upon hinge closure provide an assembly interface for KTN tetramerization. Mutational analysis using the KefC system demonstrates that this domain directly interacts with its respective transmembrane constituent, coupling ligand-mediated KTN conformational changes to the permease's activity.

Original languageEnglish
Pages (from-to)781-791
Number of pages10
JournalCell
Volume109
Issue number6
DOIs
Publication statusPublished - Jun 2002

Keywords

  • ESCHERICHIA-COLI
  • K+-CHANNEL
  • EFFLUX SYSTEM
  • PROTEIN TRKA
  • BK CHANNEL
  • TRANSPORT
  • GLUTATHIONE
  • ACTIVATION
  • DOMAIN
  • REPLACEMENT

Cite this