GSBS Student Publications
Title
Multivalent endosome targeting by homodimeric EEA1
GSBS Program
Biochemistry & Molecular Pharmacology
UMMS Affiliation
Graduate School of Biomedical Sciences; Program in Molecular Medicine and Department of Biochemistry and Molecular Pharmacology
Date
12-14-2001
Document Type
Article
Medical Subject Headings
Amino Acid Sequence; Autoantigens; Crystallography, X-Ray; Dimerization; Endosomes; Inositol Phosphates; Membrane Proteins; Models, Biological; Models, Molecular; Molecular Sequence Data; Phospholipids; Protein Binding; *Protein Structure, Quaternary; Protein Structure, Tertiary; Sequence Alignment; Vesicular Transport Proteins; Zinc Fingers; rab5 GTP-Binding Proteins
Disciplines
Life Sciences | Medicine and Health Sciences
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.
Rights and Permissions
Citation: Mol Cell. 2001 Nov;8(5):947-58.
Related Resources
Journal Title
Molecular cell
PubMed ID
11741531
Repository Citation
Dumas, John J.; Merithew, Eric Lee; Sudharshan, Eathiraj; Rajamani, Deepa; Hayes, Susan J.; Lawe, Deirdre C.; Corvera, Silvia; and Lambright, David G., "Multivalent endosome targeting by homodimeric EEA1" (2001). GSBS Student Publications. 331.
https://escholarship.umassmed.edu/gsbs_sp/331