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. GSBS Student Publications. https://doi.org/10.1016/S1097-2765(01)00385-9. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/331