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Multivalent endosome targeting by homodimeric EEA1.

J J Dumas·E Merithew·E Sudharshan·D Rajamani·S Hayes·D Lawe·S Corvera·D G Lambright
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Abstract

Early endosome autoantigen localization to early endosomes is mediated by a C-terminal region, which includes a calmodulin binding motif, a Rab5 interaction site, and a FYVE domain that selectively binds phosphatidyl inositol 3-phosphate. The crystal structure of the C-terminal region bound to inositol 1,3-bisphosphate reveals an organized, quaternary assembly consisting of a parallel coiled coil and a dyad-symmetric FYVE domain homodimer. Structural and biochemical observations support a multivalent mechanism for endosomal localization in which domain organization, dimerization, and quaternary structure amplify the weak affinity and modest specificity of head group interactions with conserved residues. A unique mode of membrane engagement deduced from the quaternary structure of the C-terminal region provides insight into the structural basis of endosome tethering.

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Amino Acid SequenceAutoantigensCrystallography, X-RayDimerizationEndosomesInositol PhosphatesMembrane ProteinsModels, BiologicalModels, MolecularMolecular Sequence DataPhospholipidsProtein BindingProtein Structure, QuaternaryProtein Structure, TertiarySequence AlignmentVesicular Transport ProteinsZinc Fingersrab5 GTP-Binding ProteinsJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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J J Dumas, E Merithew, E Sudharshan, D Rajamani, S Hayes, D Lawe, S Corvera, D G Lambright. 2001. Multivalent endosome targeting by homodimeric EEA1.. https://doi.org/10.1016/s1097-2765(01)00385-9

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