Structural mechanism of endosome docking by the FYVE domain.
The recruitment of trafficking and signaling proteins to membranes containing phosphatidylinositol 3-phosphate [PtdIns(3)P] is mediated by FYVE domains. Here, the solution structure of the FYVE domain of the early endosome antigen 1 protein (EEA1) in the free state was compared with the structures of the domain complexed with PtdIns(3)P and mixed micelles. The multistep binding mechanism involved nonspecific insertion of a hydrophobic loop into the lipid bilayer, positioning and activating the binding pocket. Ligation of PtdIns(3)P then induced a global structural change, drawing the protein termini over the bound phosphoinositide by extension of a hinge. Specific recognition of the 3-phosphate was determined indirectly and directly by two clusters of conserved arginines.
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, CO 80262, USA. tatiana.kutateladze@uchsc.edu
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D001665:Binding Sites; D018360:Crystallography, X-Ray; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D008051:Lipid Bilayers; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008823:Micelles; D008958:Models, Molecular; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D033921:Vesicular Transport Proteins
D008051:Lipid Bilayers; D008565:Membrane Proteins; D008823:Micelles; D018129:Phosphatidylinositol Phosphates; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; C055525:phosphatidylinositol 3-phosphate