Structure of the pleckstrin homology domain from beta-spectrin

Nature. 1994 Jun 23;369(6482):675-7. doi: 10.1038/369675a0.


The 'pleckstrin homology' or PH domain is a 100-residue protein module. It is present in many kinases, different isoforms of phospholipase C, GTPase-activating proteins and nucleotide-exchange factors. Its function is not known, but many proteins that contain a PH domain interact with GTP-binding proteins. The PH domain in beta-adrenergic receptor kinase may be involved in binding to the beta gamma subunits of a trimeric G-protein. We report here the three-dimensional structure of the PH domain of the cytoskeletal protein spectrin using homonuclear nuclear magnetic resonance. The core of the molecule is an antiparallel beta-sheet consisting of seven strands. The C terminus is folded into a long alpha-helix, and another helix is present in one of the surface loops. The molecule is electrostatically polarized and contains a pocket which may be involved in the binding of a ligand. There is a distant relationship to the peptidyl-prolyl-cis-trans-isomerase FKBP in which this pocket is involved in the binding of the macrocyclic compound FK506 (refs 8-11).

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blood Proteins / chemistry*
  • Computer Graphics
  • Electrochemistry
  • Escherichia coli
  • Magnetic Resonance Spectroscopy
  • Mice
  • Molecular Sequence Data
  • Phosphoproteins*
  • Protein Conformation
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Sequence Homology, Amino Acid
  • Spectrin / chemistry*


  • Blood Proteins
  • Phosphoproteins
  • Recombinant Proteins
  • platelet protein P47
  • Spectrin