Multivalent endosome targeting by homodimeric EEA1
Graduate School of Biomedical Sciences; Program in Molecular Medicine and Department of Biochemistry and Molecular Pharmacology
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
Mol Cell. 2001 Nov;8(5):947-58.
Dumas JJ, Merithew EL, Sudharshan E, Rajamani D, Hayes SJ, Lawe DC, Corvera S, Lambright DG. (2001). Multivalent endosome targeting by homodimeric EEA1. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1016/S1097-2765(01)00385-9. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/331