Janus model of the Na,K-ATPase beta-subunit transmembrane domain: distinct faces mediate alpha/beta assembly and beta-beta homo-oligomerization

J Mol Biol. 2007 Jan 19;365(3):706-14. doi: 10.1016/j.jmb.2006.10.029. Epub 2006 Oct 31.


Na,K-ATPase is a hetero-oligomer of alpha and beta-subunits. The Na,K-ATPase beta-subunit (Na,K-beta) is involved in both the regulation of ion transport activity, and in cell-cell adhesion. By structure prediction and evolutionary analysis, we identified two distinct faces on the Na,K-beta transmembrane domain (TMD) that could mediate protein-protein interactions: a glycine zipper motif and a conserved heptad repeat. Here, we show that the heptad repeat face is involved in the hetero-oligomeric interaction of Na,K-beta with Na,K-alpha, and the glycine zipper face is involved in the homo-oligomerization of Na,K-beta. Point mutations in the heptad repeat motif reduced Na,K-beta binding to Na,K-alpha, and Na,K-ATPase activity. Na,K-beta TMD homo-oligomerized in biological membranes, and mutation of the glycine zipper motif affected oligomerization and cell-cell adhesion. These results provide a structural basis for understanding how Na,K-beta links ion transport and cell-cell adhesion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Aggregation
  • Cell Membrane / enzymology
  • Dogs
  • Glycine / genetics
  • Leucine / genetics
  • Models, Molecular*
  • Molecular Sequence Data
  • Mutant Proteins / chemistry
  • Mutant Proteins / metabolism
  • Mutation / genetics
  • Protein Structure, Quaternary*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry*
  • Protein Subunits / metabolism*
  • Repetitive Sequences, Amino Acid
  • Sodium-Potassium-Exchanging ATPase / chemistry*
  • Sodium-Potassium-Exchanging ATPase / metabolism*


  • Mutant Proteins
  • Protein Subunits
  • Sodium-Potassium-Exchanging ATPase
  • Leucine
  • Glycine