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 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.
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
T G
TG
Kutateladze
K D
KD
Ogburn
W T
WT
Watson
T
T
de Beer
S D
SD
Emr
C G
CG
Burd
M
M
Overduin
D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence / Q000235:genetics; D019281:Dimerization; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012995:Solubility; D013379:Substrate Specificity; D033921:Vesicular Transport Proteins; D015032:Zinc / Q000378:metabolism; D016335:Zinc Fingers
D008081:Liposomes; D008565:Membrane Proteins; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; C055525:phosphatidylinositol 3-phosphate; D019869:Phosphatidylinositol 3-Kinases; D015032:Zinc