Phosphatidylinositol 3-phosphate recognition by the FYVE domain

Recognition of phosphatidylinositol 3-phosphate (Ptdlns(3)P) is crucial for a broad range of cellular signaling and membrane trafficking events regula ted by phosphoinositide (Pl) 3-kinases. Ptdlns(3)P binding by the FYVE doma in of human early endosome autoantigen 1 (EEA1), a protein implicated in en dosome fusion, involves two beta hairpins and an a helix. Specific amino ac ids, including those of the FYVE domain's conserved RRHHCRQCGNIF motif, con tact soluble and micelle-embedded lipid and provide specificity for Ptdlns( 3)P over Ptdlns(5)P and Ptdlns, as shown by heteronuclear magnetic resonanc e spectroscopy. Although the FYVE domain relies on a zinc-binding motif rem iniscent of RING fingers, it is distinguished by novel structural features and its Ptdlns(3)P-binding site.