Phosphatidylinositol 3-phosphate recognition by the FYVE domain

Mol Cell. 1999 Jun;3(6):805-11. doi: 10.1016/s1097-2765(01)80013-7.


Recognition of phosphatidylinositol 3-phosphate (Ptdlns(3)P) is crucial for a broad range of cellular signaling and membrane trafficking events regulated by phosphoinositide (PI) 3-kinases. PtdIns(3)P binding by the FYVE domain of human early endosome autoantigen 1 (EEA1), a protein implicated in endosome fusion, involves two beta hairpins and an alpha helix. Specific amino acids, including those of the FYVE domain's conserved RRHHCRQCGNIF motif, contact soluble and micelle-embedded lipid and provide specificity for Ptdlns(3)P over Ptdlns(5)P and Ptdlns, as shown by heteronuclear magnetic resonance spectroscopy. Although the FYVE domain relies on a zinc-binding motif reminiscent of RING fingers, it is distinguished by ovel structural features and its ptdlns(3)P-binding site.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Conserved Sequence / genetics
  • Dimerization
  • Humans
  • Liposomes / metabolism
  • Membrane Proteins / analysis
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Molecular Weight
  • Mutation
  • Nuclear Magnetic Resonance, Biomolecular
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositol Phosphates / metabolism*
  • Phosphatidylinositols / metabolism
  • Protein Binding
  • Protein Folding
  • Protein Structure, Secondary
  • Solubility
  • Substrate Specificity
  • Vesicular Transport Proteins
  • Zinc / metabolism
  • Zinc Fingers


  • Liposomes
  • Membrane Proteins
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols
  • Vesicular Transport Proteins
  • early endosome antigen 1
  • phosphatidylinositol 3-phosphate
  • Phosphatidylinositol 3-Kinases
  • Zinc