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